WEBVTT NOTE duration: "00:57:39.906" NOTE Confidence: 0.93740726 00:00:00.080 --> 00:00:01.360 Roy Herbst. Really excited to NOTE Confidence: 0.93740726 00:00:01.360 --> 00:00:02.879 introduce our ground round speaker NOTE Confidence: 0.93740726 00:00:02.879 --> 00:00:03.379 today. NOTE Confidence: 0.9930981 00:00:04.000 --> 00:00:05.839 A special pleasure to introduce NOTE Confidence: 0.9930981 00:00:05.839 --> 00:00:06.980 doctor William Oh, NOTE Confidence: 0.9843478 00:00:07.359 --> 00:00:09.280 who's just joined us. I NOTE Confidence: 0.9843478 00:00:09.280 --> 00:00:10.719 can tell you, Eric has NOTE Confidence: 0.9843478 00:00:10.719 --> 00:00:12.015 just texted me and, NOTE Confidence: 0.99541026 00:00:12.414 --> 00:00:13.615 wanted me to emphasize how NOTE Confidence: 0.99541026 00:00:13.615 --> 00:00:14.975 excited, he and we all NOTE Confidence: 0.99541026 00:00:14.975 --> 00:00:16.515 are to have William here. NOTE Confidence: 0.97755396 00:00:16.975 --> 00:00:17.935 As you'll see as I NOTE Confidence: 0.97755396 00:00:17.935 --> 00:00:19.454 introduce him, he certainly has NOTE Confidence: 0.97755396 00:00:19.454 --> 00:00:20.815 a tremendous background, and he'll NOTE Confidence: 0.97755396 00:00:20.815 --> 00:00:22.275 be a a great addition. NOTE Confidence: 0.899384 00:00:23.375 --> 00:00:24.515 Doctor O, he's NOTE Confidence: 0.99270076 00:00:25.010 --> 00:00:26.290 now the director of precision NOTE Confidence: 0.99270076 00:00:26.290 --> 00:00:27.410 medicine for the Yale Cancer NOTE Confidence: 0.99270076 00:00:27.410 --> 00:00:27.910 Center NOTE Confidence: 0.9682759 00:00:28.290 --> 00:00:29.830 and Smile Cancer Hospital. NOTE Confidence: 0.9520651 00:00:30.290 --> 00:00:31.490 He'll be very involved in NOTE Confidence: 0.9520651 00:00:31.490 --> 00:00:32.450 in in some of that NOTE Confidence: 0.9520651 00:00:32.450 --> 00:00:34.130 work and including our precision NOTE Confidence: 0.9520651 00:00:34.130 --> 00:00:35.970 medicine tumor board, and he's NOTE Confidence: 0.9520651 00:00:35.970 --> 00:00:37.570 importantly the service line medical NOTE Confidence: 0.9520651 00:00:37.570 --> 00:00:39.330 director of Smile Cancer Hospital NOTE Confidence: 0.9520651 00:00:39.330 --> 00:00:39.989 at Greenwich. NOTE Confidence: 0.9816846 00:00:40.925 --> 00:00:42.125 He received his medical degree NOTE Confidence: 0.9816846 00:00:42.125 --> 00:00:43.025 from NYU. NOTE Confidence: 0.94238913 00:00:43.645 --> 00:00:44.525 He was actually a Yale NOTE Confidence: 0.94238913 00:00:44.525 --> 00:00:45.745 undergraduate in, NOTE Confidence: 0.92351294 00:00:46.284 --> 00:00:47.185 BS in NOTE Confidence: 0.93222415 00:00:47.565 --> 00:00:49.325 molecular biophysics and biochemistry, and NOTE Confidence: 0.93222415 00:00:49.325 --> 00:00:50.705 did his internship and residency, NOTE Confidence: 0.9685677 00:00:51.245 --> 00:00:52.784 at the Brigham Women's Hospital NOTE Confidence: 0.9685677 00:00:53.085 --> 00:00:54.390 and and his clinical fellowship NOTE Confidence: 0.9685677 00:00:54.390 --> 00:00:56.149 at the, Dana Farber, which NOTE Confidence: 0.9685677 00:00:56.149 --> 00:00:57.269 is where I first met NOTE Confidence: 0.9685677 00:00:57.269 --> 00:00:57.769 him. NOTE Confidence: 0.98405266 00:00:58.469 --> 00:00:59.589 Before being at Yale, he NOTE Confidence: 0.98405266 00:00:59.589 --> 00:01:01.050 was the chief medical officer NOTE Confidence: 0.98405266 00:01:01.190 --> 00:01:02.550 and executive vice president of NOTE Confidence: 0.98405266 00:01:02.550 --> 00:01:04.090 the Prostate Cancer Foundation. NOTE Confidence: 0.96792245 00:01:04.470 --> 00:01:05.830 We focused on barriers to NOTE Confidence: 0.96792245 00:01:05.830 --> 00:01:07.590 delivery of care for prostate NOTE Confidence: 0.96792245 00:01:07.590 --> 00:01:08.650 cancer nationally. NOTE Confidence: 0.9829654 00:01:09.725 --> 00:01:11.025 William is a genitourinary NOTE Confidence: 0.99945277 00:01:11.405 --> 00:01:11.905 oncologist NOTE Confidence: 0.9562929 00:01:12.605 --> 00:01:13.965 truly with decades of experience NOTE Confidence: 0.9562929 00:01:13.965 --> 00:01:15.405 caring for patients with prostate NOTE Confidence: 0.9562929 00:01:15.405 --> 00:01:15.905 cancer. NOTE Confidence: 0.98029274 00:01:16.365 --> 00:01:17.245 For over a decade, he NOTE Confidence: 0.98029274 00:01:17.245 --> 00:01:18.605 was chief of hematology and NOTE Confidence: 0.98029274 00:01:18.605 --> 00:01:19.505 medical oncology, NOTE Confidence: 0.9502965 00:01:19.965 --> 00:01:22.125 deputy director of the, Tisch NOTE Confidence: 0.9502965 00:01:22.125 --> 00:01:23.985 Cancer Institute and NCI designated NOTE Confidence: 0.9502965 00:01:24.045 --> 00:01:25.709 center, and the Ezra Greenspan NOTE Confidence: 0.9502965 00:01:25.930 --> 00:01:27.610 professor of clinical cancer, NOTE Confidence: 0.998174 00:01:27.930 --> 00:01:28.430 therapeutics NOTE Confidence: 0.9762732 00:01:29.050 --> 00:01:30.650 at the Icahn Medical School. NOTE Confidence: 0.9762732 00:01:30.650 --> 00:01:31.790 That's Mount Sinai. NOTE Confidence: 0.9993169 00:01:32.650 --> 00:01:33.530 He has a number of NOTE Confidence: 0.9993169 00:01:33.530 --> 00:01:34.010 national, NOTE Confidence: 0.77479494 00:01:35.370 --> 00:01:35.770 you know, NOTE Confidence: 0.91878045 00:01:36.330 --> 00:01:37.690 roles that are quite relevant. NOTE Confidence: 0.91878045 00:01:37.690 --> 00:01:38.775 He's chair of the American NOTE Confidence: 0.91878045 00:01:38.775 --> 00:01:40.855 Cancer Society's National Prostate Cancer NOTE Confidence: 0.91878045 00:01:40.855 --> 00:01:41.355 Roundtable, NOTE Confidence: 0.9985487 00:01:41.735 --> 00:01:42.855 whose mission is to improve NOTE Confidence: 0.9985487 00:01:42.855 --> 00:01:44.955 prostate cancer outcomes and survivorship NOTE Confidence: 0.9793192 00:01:45.334 --> 00:01:47.015 through increasing awareness and equitable NOTE Confidence: 0.9793192 00:01:47.015 --> 00:01:48.375 access to prevention, screening, and NOTE Confidence: 0.9793192 00:01:48.375 --> 00:01:48.875 treatment. NOTE Confidence: 0.9350889 00:01:49.175 --> 00:01:49.975 He's also chair of the NOTE Confidence: 0.9350889 00:01:49.975 --> 00:01:51.575 medical advisory council for the NOTE Confidence: 0.9350889 00:01:51.575 --> 00:01:52.875 Chemotherapy Foundation. NOTE Confidence: 0.9353912 00:01:53.570 --> 00:01:55.409 So, what better way to NOTE Confidence: 0.9353912 00:01:55.409 --> 00:01:57.329 welcome William to Yale to NOTE Confidence: 0.9353912 00:01:57.329 --> 00:01:58.710 have him give grand rounds. NOTE Confidence: 0.9353912 00:01:59.009 --> 00:02:00.049 He's also part of the NOTE Confidence: 0.9353912 00:02:00.049 --> 00:02:01.890 QU division. I think Dan NOTE Confidence: 0.9353912 00:02:01.890 --> 00:02:03.270 Petrak, I know, is online, NOTE Confidence: 0.9888848 00:02:03.649 --> 00:02:04.850 from a meeting he's at, NOTE Confidence: 0.9888848 00:02:04.850 --> 00:02:05.890 and he's gonna talk to NOTE Confidence: 0.9888848 00:02:05.890 --> 00:02:07.090 us about new advances in NOTE Confidence: 0.9888848 00:02:07.090 --> 00:02:08.610 prostate cancer in twenty twenty NOTE Confidence: 0.9888848 00:02:08.610 --> 00:02:09.845 five. William, thank NOTE Confidence: 0.9849772 00:02:13.105 --> 00:02:14.385 you. Well, thank you, Roy, NOTE Confidence: 0.9849772 00:02:14.385 --> 00:02:15.264 and thank you all for NOTE Confidence: 0.9849772 00:02:15.264 --> 00:02:15.925 the welcome. NOTE Confidence: 0.95629245 00:02:19.745 --> 00:02:20.805 Let's see here. NOTE Confidence: 0.99962527 00:02:23.190 --> 00:02:24.330 These are my disclosures. NOTE Confidence: 0.99981445 00:02:27.830 --> 00:02:28.710 I wanted to talk a NOTE Confidence: 0.99981445 00:02:28.710 --> 00:02:30.150 little bit about my journey NOTE Confidence: 0.99981445 00:02:30.150 --> 00:02:30.650 here. NOTE Confidence: 0.9623715 00:02:32.230 --> 00:02:33.830 I actually worked with Roy NOTE Confidence: 0.9623715 00:02:33.830 --> 00:02:35.305 as a resident. He doesn't NOTE Confidence: 0.9623715 00:02:35.305 --> 00:02:36.745 remember that, but we were NOTE Confidence: 0.9623715 00:02:36.745 --> 00:02:37.705 residents together. He was a NOTE Confidence: 0.9623715 00:02:37.705 --> 00:02:38.505 year ahead of me. And NOTE Confidence: 0.9623715 00:02:38.505 --> 00:02:39.944 then subsequently with Eric at NOTE Confidence: 0.9623715 00:02:39.944 --> 00:02:41.065 the Dana Farber and many NOTE Confidence: 0.9623715 00:02:41.065 --> 00:02:42.745 friends. This was really key NOTE Confidence: 0.9623715 00:02:42.745 --> 00:02:44.425 to part of my journey NOTE Confidence: 0.9623715 00:02:44.425 --> 00:02:45.705 because as I moved on NOTE Confidence: 0.9623715 00:02:45.705 --> 00:02:46.605 in my career, NOTE Confidence: 0.964303 00:02:48.200 --> 00:02:49.000 as you heard, I went NOTE Confidence: 0.964303 00:02:49.000 --> 00:02:50.519 to Mount Sinai about fifteen NOTE Confidence: 0.964303 00:02:50.519 --> 00:02:51.180 years ago NOTE Confidence: 0.9711385 00:02:51.480 --> 00:02:52.360 to build a new cancer NOTE Confidence: 0.9711385 00:02:52.360 --> 00:02:53.819 center in New York City, NOTE Confidence: 0.8951658 00:02:54.120 --> 00:02:54.860 and, ultimately, NOTE Confidence: 0.99804944 00:02:55.560 --> 00:02:57.079 we did get NCI designation NOTE Confidence: 0.99804944 00:02:57.079 --> 00:02:58.379 and and renewed it. NOTE Confidence: 0.9762048 00:02:58.680 --> 00:03:00.040 A part of my goal NOTE Confidence: 0.9762048 00:03:00.040 --> 00:03:01.745 in life was to figure NOTE Confidence: 0.9762048 00:03:01.745 --> 00:03:02.945 out how we actually deliver NOTE Confidence: 0.9762048 00:03:02.945 --> 00:03:04.145 this care better to our NOTE Confidence: 0.9762048 00:03:04.145 --> 00:03:05.425 patients because so much was NOTE Confidence: 0.9762048 00:03:05.425 --> 00:03:06.805 happening and is happening. NOTE Confidence: 0.98057526 00:03:07.264 --> 00:03:07.825 So I left, NOTE Confidence: 0.9638581 00:03:08.705 --> 00:03:10.705 my my administrative roles to NOTE Confidence: 0.9638581 00:03:10.705 --> 00:03:11.985 join a company called Semaphore, NOTE Confidence: 0.9638581 00:03:11.985 --> 00:03:12.865 which was a spin out NOTE Confidence: 0.9638581 00:03:12.865 --> 00:03:14.225 of of Mount Sinai, which NOTE Confidence: 0.9638581 00:03:14.225 --> 00:03:15.585 was really using genomics, but NOTE Confidence: 0.9638581 00:03:15.585 --> 00:03:17.430 really more importantly, clinical data NOTE Confidence: 0.9638581 00:03:17.430 --> 00:03:18.650 and AI to try NOTE Confidence: 0.99872637 00:03:19.030 --> 00:03:19.690 to improve NOTE Confidence: 0.98675025 00:03:20.150 --> 00:03:21.270 the way we deliver care NOTE Confidence: 0.98675025 00:03:21.270 --> 00:03:22.870 to patients. And, this will NOTE Confidence: 0.98675025 00:03:22.870 --> 00:03:23.990 come up a little bit NOTE Confidence: 0.98675025 00:03:23.990 --> 00:03:25.510 in in my decision really NOTE Confidence: 0.98675025 00:03:25.510 --> 00:03:26.970 to come back to academia, NOTE Confidence: 0.99920684 00:03:28.150 --> 00:03:29.590 to use information and data NOTE Confidence: 0.99920684 00:03:29.590 --> 00:03:30.550 to better take care of NOTE Confidence: 0.99920684 00:03:30.550 --> 00:03:31.210 our patients. NOTE Confidence: 0.95762205 00:03:32.514 --> 00:03:33.875 It's a long story, but, NOTE Confidence: 0.9666934 00:03:34.194 --> 00:03:35.555 after two years at, a NOTE Confidence: 0.9666934 00:03:35.555 --> 00:03:37.155 publicly traded company, I I NOTE Confidence: 0.9666934 00:03:37.155 --> 00:03:38.995 joined, the Prostate Cancer Foundation NOTE Confidence: 0.9666934 00:03:38.995 --> 00:03:40.455 as the chief medical officer, NOTE Confidence: 0.99845725 00:03:41.075 --> 00:03:41.875 and I'll talk a little NOTE Confidence: 0.99845725 00:03:41.875 --> 00:03:42.915 bit about the work that NOTE Confidence: 0.99845725 00:03:42.915 --> 00:03:44.595 I did there, in today's NOTE Confidence: 0.99845725 00:03:44.595 --> 00:03:46.275 talk. But it all leads NOTE Confidence: 0.99845725 00:03:46.275 --> 00:03:47.730 to, I think, a real NOTE Confidence: 0.99845725 00:03:47.730 --> 00:03:49.010 opportunity for me to have NOTE Confidence: 0.99845725 00:03:49.010 --> 00:03:49.410 joined, NOTE Confidence: 0.8876972 00:03:49.890 --> 00:03:51.170 the Yale Cancer Center and NOTE Confidence: 0.8876972 00:03:51.170 --> 00:03:51.670 Smilow NOTE Confidence: 0.9827914 00:03:52.210 --> 00:03:53.650 to talk about work that, NOTE Confidence: 0.9827914 00:03:54.050 --> 00:03:55.490 really in two big domains. NOTE Confidence: 0.9827914 00:03:55.490 --> 00:03:56.930 One is, of course, prostate NOTE Confidence: 0.9827914 00:03:56.930 --> 00:03:57.890 cancer, which I'm gonna be NOTE Confidence: 0.9827914 00:03:57.890 --> 00:03:59.090 focusing on today, and the NOTE Confidence: 0.9827914 00:03:59.090 --> 00:04:00.614 second is how we deliver NOTE Confidence: 0.9827914 00:04:00.675 --> 00:04:01.875 the care better, not just NOTE Confidence: 0.9827914 00:04:01.875 --> 00:04:03.075 in prostate cancer, but to NOTE Confidence: 0.9827914 00:04:03.075 --> 00:04:04.595 all cancer patients, and that's NOTE Confidence: 0.9827914 00:04:04.595 --> 00:04:06.114 really that title around precision NOTE Confidence: 0.9827914 00:04:06.114 --> 00:04:06.614 medicine. NOTE Confidence: 0.9798788 00:04:07.955 --> 00:04:09.075 But today, I'm gonna focus NOTE Confidence: 0.9798788 00:04:09.075 --> 00:04:10.215 on prostate cancer. NOTE Confidence: 0.9700813 00:04:10.754 --> 00:04:11.795 These are the newest data NOTE Confidence: 0.9700813 00:04:11.795 --> 00:04:13.334 from the American Cancer Society NOTE Confidence: 0.9700813 00:04:13.394 --> 00:04:14.829 about the burden. It is NOTE Confidence: 0.9700813 00:04:14.829 --> 00:04:16.029 the number one cancer in NOTE Confidence: 0.9700813 00:04:16.029 --> 00:04:17.389 men. Really, by far, thirty NOTE Confidence: 0.9700813 00:04:17.389 --> 00:04:18.589 percent of all pros all NOTE Confidence: 0.9700813 00:04:18.589 --> 00:04:20.750 cancers are are prostate cancer. NOTE Confidence: 0.9700813 00:04:20.750 --> 00:04:21.250 And, NOTE Confidence: 0.9875966 00:04:21.710 --> 00:04:23.229 interestingly, even though we sometimes NOTE Confidence: 0.9875966 00:04:23.229 --> 00:04:24.430 have a belief that prostate NOTE Confidence: 0.9875966 00:04:24.430 --> 00:04:25.710 cancer is not lethal, it's NOTE Confidence: 0.9875966 00:04:25.710 --> 00:04:27.070 still the second leading cause NOTE Confidence: 0.9875966 00:04:27.070 --> 00:04:28.545 of cancer death. Not only NOTE Confidence: 0.9875966 00:04:28.545 --> 00:04:29.665 that, the death rate is NOTE Confidence: 0.9875966 00:04:29.665 --> 00:04:30.485 actually rising. NOTE Confidence: 0.9988876 00:04:30.865 --> 00:04:31.904 This is as of twenty NOTE Confidence: 0.9988876 00:04:31.904 --> 00:04:32.725 twenty five. NOTE Confidence: 0.9711279 00:04:35.585 --> 00:04:37.105 Here's the incidence rates, and NOTE Confidence: 0.9711279 00:04:37.105 --> 00:04:38.545 it this is, again, really NOTE Confidence: 0.9711279 00:04:38.545 --> 00:04:39.745 hot off the press. And NOTE Confidence: 0.9711279 00:04:39.745 --> 00:04:40.785 you can see this very NOTE Confidence: 0.9711279 00:04:40.785 --> 00:04:43.479 sharp, increase in the, incidence NOTE Confidence: 0.9711279 00:04:43.479 --> 00:04:45.080 of prostate cancer. This is NOTE Confidence: 0.9711279 00:04:45.080 --> 00:04:46.120 in in and of itself NOTE Confidence: 0.9711279 00:04:46.120 --> 00:04:47.960 quite an interesting conversation about NOTE Confidence: 0.9711279 00:04:47.960 --> 00:04:48.460 why NOTE Confidence: 0.9725354 00:04:48.839 --> 00:04:50.199 it's risen so sharply in NOTE Confidence: 0.9725354 00:04:50.199 --> 00:04:51.080 the past decade. NOTE Confidence: 0.9743373 00:04:51.720 --> 00:04:52.520 And we can talk a NOTE Confidence: 0.9743373 00:04:52.520 --> 00:04:53.479 little bit more in the NOTE Confidence: 0.9743373 00:04:53.479 --> 00:04:54.824 q and a about what NOTE Confidence: 0.9743373 00:04:54.824 --> 00:04:56.185 the in implications there. And NOTE Confidence: 0.9743373 00:04:56.185 --> 00:04:57.145 you can see the parallel NOTE Confidence: 0.9743373 00:04:57.145 --> 00:04:58.264 in breast cancer, the breast NOTE Confidence: 0.9743373 00:04:58.264 --> 00:04:59.805 cancer incidence rates rising. NOTE Confidence: 0.96795595 00:05:02.904 --> 00:05:03.865 But the death rate from NOTE Confidence: 0.96795595 00:05:03.865 --> 00:05:05.544 prostate cancer has, in fact, NOTE Confidence: 0.96795595 00:05:05.544 --> 00:05:06.044 plateaued, NOTE Confidence: 0.9688571 00:05:06.505 --> 00:05:07.224 and there's a lot of NOTE Confidence: 0.9688571 00:05:07.224 --> 00:05:08.479 reasons to be concerned about NOTE Confidence: 0.9688571 00:05:08.479 --> 00:05:09.919 this plateau. You know, early NOTE Confidence: 0.9688571 00:05:09.919 --> 00:05:10.880 when I started in this NOTE Confidence: 0.9688571 00:05:10.880 --> 00:05:12.560 field about, twenty five years NOTE Confidence: 0.9688571 00:05:12.560 --> 00:05:14.160 ago, I thought the prostate NOTE Confidence: 0.9688571 00:05:14.160 --> 00:05:15.520 cancer would actually if you NOTE Confidence: 0.9688571 00:05:15.520 --> 00:05:16.800 see this drop that that NOTE Confidence: 0.9688571 00:05:16.800 --> 00:05:17.680 you can see on this NOTE Confidence: 0.9688571 00:05:17.680 --> 00:05:19.199 graph, I thought prostate cancer NOTE Confidence: 0.9688571 00:05:19.199 --> 00:05:21.060 would fall below colo colorectal NOTE Confidence: 0.9688571 00:05:21.199 --> 00:05:22.639 and other can cancer death NOTE Confidence: 0.9688571 00:05:22.639 --> 00:05:24.055 rates, but in fact, it NOTE Confidence: 0.9688571 00:05:24.055 --> 00:05:25.415 has plateaued and in as NOTE Confidence: 0.9688571 00:05:25.415 --> 00:05:26.855 I mentioned, it's slowly rising. NOTE Confidence: 0.9688571 00:05:26.855 --> 00:05:27.975 Of course, lung cancer death NOTE Confidence: 0.9688571 00:05:27.975 --> 00:05:29.275 rates have gone down dramatically NOTE Confidence: 0.9688571 00:05:29.335 --> 00:05:31.255 in men since, the surgeon NOTE Confidence: 0.9688571 00:05:31.255 --> 00:05:33.575 general's report around, around cigarette NOTE Confidence: 0.9688571 00:05:33.575 --> 00:05:34.075 smoking. NOTE Confidence: 0.97778225 00:05:35.415 --> 00:05:36.294 And these are some of NOTE Confidence: 0.97778225 00:05:36.294 --> 00:05:37.750 the data that have recently NOTE Confidence: 0.97778225 00:05:37.750 --> 00:05:39.349 come out about why we're NOTE Confidence: 0.97778225 00:05:39.349 --> 00:05:40.629 concerned about the death rate NOTE Confidence: 0.97778225 00:05:40.629 --> 00:05:41.449 actually rising. NOTE Confidence: 0.9841736 00:05:41.909 --> 00:05:42.810 If you look at, NOTE Confidence: 0.96478033 00:05:43.669 --> 00:05:45.349 the rates of, cancer, you NOTE Confidence: 0.96478033 00:05:45.349 --> 00:05:47.050 can see again that rise NOTE Confidence: 0.96478033 00:05:47.270 --> 00:05:48.629 both both in all groups, NOTE Confidence: 0.96478033 00:05:48.629 --> 00:05:50.069 but also specifically in black NOTE Confidence: 0.96478033 00:05:50.069 --> 00:05:51.694 men who are denoted by NOTE Confidence: 0.96478033 00:05:51.694 --> 00:05:53.615 the green dots here. But NOTE Confidence: 0.96478033 00:05:53.615 --> 00:05:55.055 particularly, I wanna point out, NOTE Confidence: 0.96478033 00:05:55.455 --> 00:05:57.294 this this graph, the the NOTE Confidence: 0.96478033 00:05:57.294 --> 00:05:59.455 distant, metastatic disease, and you NOTE Confidence: 0.96478033 00:05:59.455 --> 00:06:00.574 can see two things here. NOTE Confidence: 0.96478033 00:06:00.574 --> 00:06:01.615 One is the rate of NOTE Confidence: 0.96478033 00:06:01.615 --> 00:06:03.714 metastatic prostate cancer is growing NOTE Confidence: 0.96478033 00:06:03.935 --> 00:06:05.375 quite dramatically over the past NOTE Confidence: 0.96478033 00:06:05.375 --> 00:06:05.875 decade. NOTE Confidence: 0.9475912 00:06:06.589 --> 00:06:07.790 And one question is why? NOTE Confidence: 0.9475912 00:06:07.790 --> 00:06:08.670 This is in the US. NOTE Confidence: 0.9475912 00:06:08.670 --> 00:06:09.870 This is not worldwide. This NOTE Confidence: 0.9475912 00:06:09.870 --> 00:06:11.230 is in a country where NOTE Confidence: 0.9475912 00:06:11.230 --> 00:06:12.430 you could see that, that NOTE Confidence: 0.9475912 00:06:12.430 --> 00:06:13.630 rates of metastatic disease were NOTE Confidence: 0.9475912 00:06:13.630 --> 00:06:14.130 dramatically NOTE Confidence: 0.9974518 00:06:14.589 --> 00:06:15.570 dropping before, NOTE Confidence: 0.9795769 00:06:17.390 --> 00:06:18.670 before this point. So what's NOTE Confidence: 0.9795769 00:06:18.670 --> 00:06:19.950 happened over the past decade? NOTE Confidence: 0.9795769 00:06:19.950 --> 00:06:21.225 And then you still see NOTE Confidence: 0.9795769 00:06:21.225 --> 00:06:23.065 this huge disparity between black NOTE Confidence: 0.9795769 00:06:23.065 --> 00:06:24.285 men and all other races. NOTE Confidence: 0.9536743 00:06:24.745 --> 00:06:25.625 And this is gonna get NOTE Confidence: 0.9536743 00:06:25.625 --> 00:06:26.505 at some of the work NOTE Confidence: 0.9536743 00:06:26.505 --> 00:06:27.464 that I did, particularly at NOTE Confidence: 0.9536743 00:06:27.464 --> 00:06:28.925 the prostate cancer foundation. NOTE Confidence: 0.9977741 00:06:29.545 --> 00:06:30.904 But, I think a lot NOTE Confidence: 0.9977741 00:06:30.904 --> 00:06:32.105 of us are concerned about NOTE Confidence: 0.9977741 00:06:32.105 --> 00:06:33.464 these these trends about and NOTE Confidence: 0.9977741 00:06:33.464 --> 00:06:35.005 about how we reverse them. NOTE Confidence: 0.90485024 00:06:36.060 --> 00:06:37.500 Also last year, the Lancet NOTE Confidence: 0.90485024 00:06:37.500 --> 00:06:39.199 Commission published a report NOTE Confidence: 0.98965424 00:06:39.980 --> 00:06:41.660 about worldwide rates of of NOTE Confidence: 0.98965424 00:06:41.660 --> 00:06:43.339 prostate cancer. And what we NOTE Confidence: 0.98965424 00:06:43.339 --> 00:06:44.460 know is that over the NOTE Confidence: 0.98965424 00:06:44.460 --> 00:06:46.060 next twenty years or so, NOTE Confidence: 0.98965424 00:06:46.060 --> 00:06:47.339 from twenty twenty to twenty, NOTE Confidence: 0.98965424 00:06:47.740 --> 00:06:49.020 forty, you can see in NOTE Confidence: 0.98965424 00:06:49.020 --> 00:06:50.300 the in the corners here, NOTE Confidence: 0.98965424 00:06:50.300 --> 00:06:51.199 the rates of NOTE Confidence: 0.9930671 00:06:51.555 --> 00:06:53.555 prostate cancer will double. So NOTE Confidence: 0.9930671 00:06:53.555 --> 00:06:54.515 the number of new cases NOTE Confidence: 0.9930671 00:06:54.515 --> 00:06:55.714 will double, and the number NOTE Confidence: 0.9930671 00:06:55.714 --> 00:06:57.154 of deaths will increase by NOTE Confidence: 0.9930671 00:06:57.154 --> 00:06:58.595 eighty five percent. And you NOTE Confidence: 0.9930671 00:06:58.595 --> 00:06:59.395 can see a lot of NOTE Confidence: 0.9930671 00:06:59.395 --> 00:07:00.515 it is driven in the NOTE Confidence: 0.9930671 00:07:00.515 --> 00:07:01.015 orange NOTE Confidence: 0.9740294 00:07:01.475 --> 00:07:03.335 bars by by East Asia, NOTE Confidence: 0.99744 00:07:03.635 --> 00:07:04.375 South America, NOTE Confidence: 0.9522116 00:07:05.650 --> 00:07:07.089 and, and other parts of NOTE Confidence: 0.9522116 00:07:07.089 --> 00:07:08.289 the world. So we're seeing NOTE Confidence: 0.9522116 00:07:08.289 --> 00:07:09.750 both an increase in incidence, NOTE Confidence: 0.9522116 00:07:09.810 --> 00:07:10.470 but also, NOTE Confidence: 0.9656104 00:07:11.009 --> 00:07:12.449 a significant increase in death NOTE Confidence: 0.9656104 00:07:12.449 --> 00:07:13.650 rates. And, again, we can NOTE Confidence: 0.9656104 00:07:13.650 --> 00:07:15.250 debate and discuss some of NOTE Confidence: 0.9656104 00:07:15.250 --> 00:07:16.930 the underlying causes of this. NOTE Confidence: 0.9656104 00:07:17.169 --> 00:07:18.050 This is not just a NOTE Confidence: 0.9656104 00:07:18.050 --> 00:07:19.830 detection issue. This is a NOTE Confidence: 0.9656104 00:07:19.970 --> 00:07:21.110 a a a true concern, NOTE Confidence: 0.9656104 00:07:21.305 --> 00:07:22.345 especially in an era where NOTE Confidence: 0.9656104 00:07:22.345 --> 00:07:23.305 we have so many new NOTE Confidence: 0.9656104 00:07:23.305 --> 00:07:24.345 therapies, which is what I'm NOTE Confidence: 0.9656104 00:07:24.345 --> 00:07:26.125 gonna shift my talk to. NOTE Confidence: 0.99902916 00:07:27.225 --> 00:07:28.605 So I'm gonna talk about NOTE Confidence: 0.99902916 00:07:28.665 --> 00:07:30.125 five different areas today. NOTE Confidence: 0.9823654 00:07:30.585 --> 00:07:31.465 I know that's a lot NOTE Confidence: 0.9823654 00:07:31.465 --> 00:07:33.065 to cover in a forty NOTE Confidence: 0.9823654 00:07:33.065 --> 00:07:34.345 five, fifty minute talk, but NOTE Confidence: 0.9823654 00:07:34.345 --> 00:07:35.385 I wanna I'm gonna go NOTE Confidence: 0.9823654 00:07:35.385 --> 00:07:36.200 through these because I wanted NOTE Confidence: 0.9823654 00:07:36.200 --> 00:07:37.080 to just give you a NOTE Confidence: 0.9823654 00:07:37.080 --> 00:07:38.860 sense of how much new NOTE Confidence: 0.9823654 00:07:38.920 --> 00:07:40.200 information and new data and NOTE Confidence: 0.9823654 00:07:40.200 --> 00:07:41.740 new treatments are really happening. NOTE Confidence: 0.9823654 00:07:41.880 --> 00:07:42.760 But I'm gonna start with NOTE Confidence: 0.9823654 00:07:42.760 --> 00:07:44.140 this idea that screening NOTE Confidence: 0.8904114 00:07:44.840 --> 00:07:46.440 is bad for prostate cancer. NOTE Confidence: 0.8904114 00:07:46.440 --> 00:07:47.340 And this is unfortunately NOTE Confidence: 0.97565126 00:07:47.960 --> 00:07:49.660 something that has, taken NOTE Confidence: 0.9671991 00:07:50.035 --> 00:07:51.715 hold and may be explaining NOTE Confidence: 0.9671991 00:07:51.715 --> 00:07:53.315 some of the epidemiologic trends NOTE Confidence: 0.9671991 00:07:53.315 --> 00:07:54.215 that you're seeing. NOTE Confidence: 0.9835717 00:07:54.755 --> 00:07:56.355 What is risk adapted screening? NOTE Confidence: 0.9835717 00:07:56.355 --> 00:07:57.715 Well, I think part of NOTE Confidence: 0.9835717 00:07:57.715 --> 00:07:58.375 this is, NOTE Confidence: 0.99911404 00:07:59.555 --> 00:08:01.335 conveyed by a very famous, NOTE Confidence: 0.937886 00:08:02.035 --> 00:08:03.155 urologist who is a chair NOTE Confidence: 0.937886 00:08:03.155 --> 00:08:04.675 of urology at, Memorial Sloan NOTE Confidence: 0.937886 00:08:04.675 --> 00:08:06.090 Kettering for many years, and, NOTE Confidence: 0.937886 00:08:06.090 --> 00:08:08.010 unfortunately, himself died of prostate NOTE Confidence: 0.937886 00:08:08.010 --> 00:08:09.050 cancer. But he had a NOTE Confidence: 0.937886 00:08:09.050 --> 00:08:11.130 lot of, wisdom that he NOTE Confidence: 0.937886 00:08:11.130 --> 00:08:12.670 would talk about. One was, NOTE Confidence: 0.937886 00:08:12.890 --> 00:08:14.090 he said, growing old is NOTE Confidence: 0.937886 00:08:14.090 --> 00:08:15.930 invariably fatal. Prostate cancer is NOTE Confidence: 0.937886 00:08:15.930 --> 00:08:17.770 less so. This gets to, NOTE Confidence: 0.937886 00:08:17.770 --> 00:08:19.050 from the nineteen seventies and NOTE Confidence: 0.937886 00:08:19.050 --> 00:08:20.090 eighties, the idea that not NOTE Confidence: 0.937886 00:08:20.090 --> 00:08:21.710 all prostate cancers are lethal. NOTE Confidence: 0.95003 00:08:22.865 --> 00:08:24.065 The other, thing that he NOTE Confidence: 0.95003 00:08:24.065 --> 00:08:25.825 said is, is cure possible NOTE Confidence: 0.95003 00:08:25.825 --> 00:08:27.025 for though in those for NOTE Confidence: 0.95003 00:08:27.025 --> 00:08:28.465 whom it is necessary, and NOTE Confidence: 0.95003 00:08:28.465 --> 00:08:29.445 is cure necessary NOTE Confidence: 0.9902854 00:08:29.905 --> 00:08:30.785 for those in whom it NOTE Confidence: 0.9902854 00:08:30.785 --> 00:08:31.905 is possible? What he's talking NOTE Confidence: 0.9902854 00:08:31.905 --> 00:08:33.345 about is the heterogeneity of NOTE Confidence: 0.9902854 00:08:33.345 --> 00:08:34.785 prostate cancer means that some NOTE Confidence: 0.9902854 00:08:34.785 --> 00:08:36.245 men should be left alone NOTE Confidence: 0.9935329 00:08:36.630 --> 00:08:37.990 to live their lives without NOTE Confidence: 0.9935329 00:08:37.990 --> 00:08:39.670 intervention, and other men, no NOTE Confidence: 0.9935329 00:08:39.670 --> 00:08:40.870 matter what we do, may NOTE Confidence: 0.9935329 00:08:40.870 --> 00:08:41.990 progress and die of their NOTE Confidence: 0.9935329 00:08:41.990 --> 00:08:43.190 disease. So when you think NOTE Confidence: 0.9935329 00:08:43.190 --> 00:08:44.230 of a disease with such NOTE Confidence: 0.9935329 00:08:44.230 --> 00:08:44.730 heterogeneity, NOTE Confidence: 0.9990035 00:08:45.270 --> 00:08:46.309 how do we apply the NOTE Confidence: 0.9990035 00:08:46.309 --> 00:08:47.670 right treatments and the right NOTE Confidence: 0.9990035 00:08:47.670 --> 00:08:48.870 solutions to each of these NOTE Confidence: 0.9990035 00:08:48.870 --> 00:08:49.370 patients? NOTE Confidence: 0.92817897 00:08:50.925 --> 00:08:52.125 So we we wrote an NOTE Confidence: 0.92817897 00:08:52.125 --> 00:08:53.965 editorial. This is Sigrid Carlson NOTE Confidence: 0.92817897 00:08:53.965 --> 00:08:55.805 and I really talking about, NOTE Confidence: 0.9769565 00:08:56.285 --> 00:08:58.045 screening guidelines, and and you NOTE Confidence: 0.9769565 00:08:58.045 --> 00:08:59.005 don't you're not meant to NOTE Confidence: 0.9769565 00:08:59.005 --> 00:09:00.365 read this. I can tell NOTE Confidence: 0.9769565 00:09:00.365 --> 00:09:01.645 you just just that all NOTE Confidence: 0.9769565 00:09:01.645 --> 00:09:03.485 of the major organizations that NOTE Confidence: 0.9769565 00:09:03.485 --> 00:09:05.105 actually put out screening guidelines, NOTE Confidence: 0.9256564 00:09:05.670 --> 00:09:07.510 put out slightly different ones. NOTE Confidence: 0.9256564 00:09:07.510 --> 00:09:08.890 So this is very complicated NOTE Confidence: 0.9256564 00:09:09.029 --> 00:09:10.490 and unfortunately on the line. NOTE Confidence: 0.9256564 00:09:10.550 --> 00:09:12.070 Now most primary care doctors NOTE Confidence: 0.9256564 00:09:12.070 --> 00:09:13.370 and most insurance companies, NOTE Confidence: 0.96368635 00:09:13.990 --> 00:09:15.270 fund the recommendations of the NOTE Confidence: 0.96368635 00:09:15.270 --> 00:09:16.950 US Preventative Services Task Force, NOTE Confidence: 0.96368635 00:09:16.950 --> 00:09:17.770 but the AUA, NOTE Confidence: 0.9855115 00:09:18.295 --> 00:09:19.895 the American Cancer Society, the NOTE Confidence: 0.9855115 00:09:19.895 --> 00:09:21.575 American Society of Clinical Oncology, NOTE Confidence: 0.9855115 00:09:21.575 --> 00:09:23.015 NCCN, they all put out NOTE Confidence: 0.9855115 00:09:23.015 --> 00:09:24.455 different guidelines. And you can NOTE Confidence: 0.9855115 00:09:24.455 --> 00:09:25.655 see if you dig into NOTE Confidence: 0.9855115 00:09:25.655 --> 00:09:27.975 this editorial that, unfortunately, all NOTE Confidence: 0.9855115 00:09:27.975 --> 00:09:30.235 of the guidelines differ slightly. NOTE Confidence: 0.9840974 00:09:30.660 --> 00:09:32.179 And, you know, who's not NOTE Confidence: 0.9840974 00:09:32.179 --> 00:09:33.220 gonna be confused when you NOTE Confidence: 0.9840974 00:09:33.220 --> 00:09:34.600 see all of this, variation NOTE Confidence: 0.9840974 00:09:34.660 --> 00:09:35.620 in terms of the the NOTE Confidence: 0.9840974 00:09:35.620 --> 00:09:36.120 guidelines? NOTE Confidence: 0.992596 00:09:37.940 --> 00:09:38.740 So when I joined the NOTE Confidence: 0.992596 00:09:38.740 --> 00:09:40.260 Prostate Cancer Foundation a few NOTE Confidence: 0.992596 00:09:40.260 --> 00:09:41.860 years ago, even though I'm NOTE Confidence: 0.992596 00:09:41.860 --> 00:09:42.839 a medical oncologist NOTE Confidence: 0.9764657 00:09:43.155 --> 00:09:44.675 and I don't necessarily screen NOTE Confidence: 0.9764657 00:09:44.675 --> 00:09:45.875 patients, I I asked the NOTE Confidence: 0.9764657 00:09:45.875 --> 00:09:47.075 question, where can I make NOTE Confidence: 0.9764657 00:09:47.075 --> 00:09:48.675 the biggest difference in terms NOTE Confidence: 0.9764657 00:09:48.675 --> 00:09:49.175 of, NOTE Confidence: 0.9867091 00:09:49.635 --> 00:09:51.555 reducing mortality from from from NOTE Confidence: 0.9867091 00:09:51.555 --> 00:09:53.155 prostate cancer? So one of NOTE Confidence: 0.9867091 00:09:53.155 --> 00:09:54.355 the first areas was this NOTE Confidence: 0.9867091 00:09:54.355 --> 00:09:56.055 concept of risk adapted screening. NOTE Confidence: 0.9867091 00:09:56.339 --> 00:09:57.220 So we know, as I NOTE Confidence: 0.9867091 00:09:57.220 --> 00:09:58.600 showed you in that earlier NOTE Confidence: 0.9867091 00:09:58.740 --> 00:09:59.240 epidemiologic NOTE Confidence: 0.9826584 00:09:59.620 --> 00:10:01.459 graph, black men are one NOTE Confidence: 0.9826584 00:10:01.459 --> 00:10:02.579 of the groups that has NOTE Confidence: 0.9826584 00:10:02.579 --> 00:10:04.019 the highest rate of both NOTE Confidence: 0.9826584 00:10:04.019 --> 00:10:05.540 diagnosis and death from cancer, NOTE Confidence: 0.9826584 00:10:05.540 --> 00:10:06.339 and you can see that NOTE Confidence: 0.9826584 00:10:06.339 --> 00:10:07.699 here. They actually have about NOTE Confidence: 0.9826584 00:10:07.699 --> 00:10:08.740 a two point two fold NOTE Confidence: 0.9826584 00:10:08.740 --> 00:10:09.860 higher risk of dying of NOTE Confidence: 0.9826584 00:10:09.860 --> 00:10:11.635 prostate cancer. They present at NOTE Confidence: 0.9826584 00:10:11.635 --> 00:10:13.235 younger ages, they have more NOTE Confidence: 0.9826584 00:10:13.235 --> 00:10:14.355 aggressive disease, and are more NOTE Confidence: 0.9826584 00:10:14.355 --> 00:10:15.635 likely to be diagnosed with NOTE Confidence: 0.9826584 00:10:15.635 --> 00:10:16.455 advanced disease. NOTE Confidence: 0.98629683 00:10:16.835 --> 00:10:18.775 So these racial disparities clearly NOTE Confidence: 0.98629683 00:10:18.835 --> 00:10:20.275 exist, and this is clearly NOTE Confidence: 0.98629683 00:10:20.275 --> 00:10:21.735 a population at risk. NOTE Confidence: 0.98041874 00:10:22.195 --> 00:10:24.115 Now, there's an interesting conversation NOTE Confidence: 0.98041874 00:10:24.115 --> 00:10:25.654 about the biology and genetics NOTE Confidence: 0.98041874 00:10:25.714 --> 00:10:27.040 behind this and whether this NOTE Confidence: 0.98041874 00:10:27.040 --> 00:10:28.580 is truly an access issue, NOTE Confidence: 0.98041874 00:10:28.800 --> 00:10:30.480 a socioeconomic issue, or if NOTE Confidence: 0.98041874 00:10:30.480 --> 00:10:32.180 it's truly a biological issue. NOTE Confidence: 0.98041874 00:10:32.320 --> 00:10:33.360 But the bottom line is NOTE Confidence: 0.98041874 00:10:33.360 --> 00:10:34.800 the self reported black men NOTE Confidence: 0.98041874 00:10:34.800 --> 00:10:35.760 have the highest rates of NOTE Confidence: 0.98041874 00:10:35.760 --> 00:10:37.440 dying of prostate cancer, in NOTE Confidence: 0.98041874 00:10:37.440 --> 00:10:38.834 the United States and and NOTE Confidence: 0.98041874 00:10:38.834 --> 00:10:39.814 actually in the world. NOTE Confidence: 0.9852213 00:10:40.115 --> 00:10:41.154 So what we did was NOTE Confidence: 0.9852213 00:10:41.154 --> 00:10:42.915 we simply created a, NOTE Confidence: 0.9730094 00:10:43.394 --> 00:10:44.834 an expert group, a panel NOTE Confidence: 0.9730094 00:10:44.834 --> 00:10:45.334 here, NOTE Confidence: 0.9998096 00:10:45.875 --> 00:10:47.254 to review the evidence. NOTE Confidence: 0.9847621 00:10:47.554 --> 00:10:48.995 Now the issue is that NOTE Confidence: 0.9847621 00:10:48.995 --> 00:10:50.214 if you try to only, NOTE Confidence: 0.99674684 00:10:50.675 --> 00:10:52.535 limit that evidence to randomized NOTE Confidence: 0.9792015 00:10:53.160 --> 00:10:54.860 phase three trials, you'll be, NOTE Confidence: 0.97611576 00:10:55.399 --> 00:10:57.240 very disappointed because of the NOTE Confidence: 0.97611576 00:10:57.240 --> 00:10:58.679 three randomized trials that have NOTE Confidence: 0.97611576 00:10:58.679 --> 00:11:00.120 looked at screening, only five NOTE Confidence: 0.97611576 00:11:00.120 --> 00:11:01.240 percent of one of the NOTE Confidence: 0.97611576 00:11:01.240 --> 00:11:03.559 three trials actually had, black NOTE Confidence: 0.97611576 00:11:03.559 --> 00:11:05.240 men enrolled. So here's a NOTE Confidence: 0.97611576 00:11:05.240 --> 00:11:07.079 high risk population who have NOTE Confidence: 0.97611576 00:11:07.079 --> 00:11:08.425 just not been studied. So NOTE Confidence: 0.97611576 00:11:08.425 --> 00:11:09.625 is the absence of evidence, NOTE Confidence: 0.97611576 00:11:09.625 --> 00:11:10.505 does that mean that we NOTE Confidence: 0.97611576 00:11:10.505 --> 00:11:12.585 shouldn't actually make recommendations that NOTE Confidence: 0.97611576 00:11:12.585 --> 00:11:14.665 directly impact this population? And NOTE Confidence: 0.97611576 00:11:14.665 --> 00:11:15.945 we decided no. We said NOTE Confidence: 0.97611576 00:11:15.945 --> 00:11:16.985 we were gonna look at NOTE Confidence: 0.97611576 00:11:16.985 --> 00:11:18.184 all the evidence, but include NOTE Confidence: 0.97611576 00:11:18.184 --> 00:11:19.245 evidence that included NOTE Confidence: 0.998521 00:11:19.545 --> 00:11:21.645 modeling evidence and observational data. NOTE Confidence: 0.91697073 00:11:22.660 --> 00:11:23.780 So this paper was published NOTE Confidence: 0.91697073 00:11:23.780 --> 00:11:25.220 in the NEJM Evidence last NOTE Confidence: 0.91697073 00:11:25.220 --> 00:11:26.740 year, and it asked six NOTE Confidence: 0.91697073 00:11:26.740 --> 00:11:28.340 questions. You know, should black NOTE Confidence: 0.91697073 00:11:28.340 --> 00:11:29.240 men be screened? NOTE Confidence: 0.92855287 00:11:29.540 --> 00:11:30.660 What should they know about NOTE Confidence: 0.92855287 00:11:30.660 --> 00:11:32.179 screening? At what age and NOTE Confidence: 0.92855287 00:11:32.179 --> 00:11:33.300 so on? And I'm not NOTE Confidence: 0.92855287 00:11:33.300 --> 00:11:34.740 gonna go into detail about NOTE Confidence: 0.92855287 00:11:34.740 --> 00:11:35.720 all this, but, basically, NOTE Confidence: 0.9980646 00:11:36.125 --> 00:11:37.245 most men are recommended to NOTE Confidence: 0.9980646 00:11:37.245 --> 00:11:38.204 have screening at the age NOTE Confidence: 0.9980646 00:11:38.204 --> 00:11:39.665 of fifty to fifty five. NOTE Confidence: 0.9719545 00:11:40.365 --> 00:11:41.804 And even though the guidelines NOTE Confidence: 0.9719545 00:11:41.804 --> 00:11:43.404 have always put a black NOTE Confidence: 0.9719545 00:11:43.404 --> 00:11:45.024 man into an asterisk category, NOTE Confidence: 0.9719545 00:11:45.084 --> 00:11:45.885 we took it out of NOTE Confidence: 0.9719545 00:11:45.885 --> 00:11:46.925 the asterisk, and we just NOTE Confidence: 0.9719545 00:11:46.925 --> 00:11:48.445 basically said black men should NOTE Confidence: 0.9719545 00:11:48.445 --> 00:11:49.964 get a baseline PSA between NOTE Confidence: 0.9719545 00:11:49.964 --> 00:11:50.925 the ages of forty and NOTE Confidence: 0.9719545 00:11:50.925 --> 00:11:52.199 forty five, and they should NOTE Confidence: 0.9719545 00:11:52.199 --> 00:11:53.800 also get annual screening. I NOTE Confidence: 0.9719545 00:11:53.800 --> 00:11:55.100 think there's a real opportunity, NOTE Confidence: 0.9273393 00:11:55.879 --> 00:11:56.779 certainly nationally, NOTE Confidence: 0.9773639 00:11:57.160 --> 00:11:59.240 but also here, within the, NOTE Confidence: 0.9773639 00:11:59.639 --> 00:12:00.920 the Yale network to really NOTE Confidence: 0.9773639 00:12:00.920 --> 00:12:01.879 think about how we can NOTE Confidence: 0.9773639 00:12:01.879 --> 00:12:03.399 have an impact on on NOTE Confidence: 0.9773639 00:12:03.399 --> 00:12:04.279 patients who are at the NOTE Confidence: 0.9773639 00:12:04.279 --> 00:12:06.055 highest risk of both getting NOTE Confidence: 0.9773639 00:12:06.055 --> 00:12:07.495 prostate cancer but also dying NOTE Confidence: 0.9773639 00:12:07.495 --> 00:12:08.235 of it. NOTE Confidence: 0.94340134 00:12:09.735 --> 00:12:11.575 But as I mentioned earlier, NOTE Confidence: 0.94340134 00:12:11.575 --> 00:12:12.855 some of the challenges here NOTE Confidence: 0.94340134 00:12:12.855 --> 00:12:13.655 are how do we actually NOTE Confidence: 0.94340134 00:12:13.655 --> 00:12:14.795 deliver this care. NOTE Confidence: 0.9844502 00:12:15.495 --> 00:12:17.355 So, when I left PCF, NOTE Confidence: 0.978293 00:12:18.135 --> 00:12:19.490 really, it was to, as NOTE Confidence: 0.978293 00:12:19.490 --> 00:12:20.610 I thought about coming back NOTE Confidence: 0.978293 00:12:20.610 --> 00:12:22.149 to an academic medical center, NOTE Confidence: 0.978293 00:12:22.209 --> 00:12:23.649 it really requires this kind NOTE Confidence: 0.978293 00:12:23.649 --> 00:12:25.490 of partnership, really community leaders NOTE Confidence: 0.978293 00:12:25.490 --> 00:12:27.329 and academic centers. And I NOTE Confidence: 0.978293 00:12:27.329 --> 00:12:28.529 think that, one of the NOTE Confidence: 0.978293 00:12:28.529 --> 00:12:30.370 organizations that I've been fortunate NOTE Confidence: 0.978293 00:12:30.370 --> 00:12:31.455 to be asked to to NOTE Confidence: 0.978293 00:12:31.455 --> 00:12:32.835 join and lead is the NOTE Confidence: 0.978293 00:12:32.895 --> 00:12:34.995 ACS National Prostate Cancer Roundtable. NOTE Confidence: 0.9895652 00:12:35.775 --> 00:12:37.135 And the idea really is NOTE Confidence: 0.9895652 00:12:37.135 --> 00:12:38.335 to think about projects that NOTE Confidence: 0.9895652 00:12:38.335 --> 00:12:39.875 will actually impact, NOTE Confidence: 0.9826347 00:12:40.415 --> 00:12:41.615 the disease in the exact NOTE Confidence: 0.9826347 00:12:41.615 --> 00:12:42.655 way that I I first NOTE Confidence: 0.9826347 00:12:42.655 --> 00:12:44.115 started when I joined PCF. NOTE Confidence: 0.98943174 00:12:44.709 --> 00:12:45.990 And so this started in NOTE Confidence: 0.98943174 00:12:45.990 --> 00:12:47.110 September. More to come on NOTE Confidence: 0.98943174 00:12:47.110 --> 00:12:48.550 this, and I'd love to NOTE Confidence: 0.98943174 00:12:48.550 --> 00:12:49.910 interact with the community here NOTE Confidence: 0.98943174 00:12:49.910 --> 00:12:50.870 to think about ways in NOTE Confidence: 0.98943174 00:12:50.870 --> 00:12:51.929 which we can actually, NOTE Confidence: 0.9713755 00:12:52.550 --> 00:12:54.070 address this at risk population. NOTE Confidence: 0.9713755 00:12:54.070 --> 00:12:55.190 There are other at risk NOTE Confidence: 0.9713755 00:12:55.190 --> 00:12:56.630 populations. For example, those with NOTE Confidence: 0.9713755 00:12:56.630 --> 00:12:57.830 a family history or genetic NOTE Confidence: 0.9713755 00:12:57.830 --> 00:12:59.215 risk, Not gonna have a NOTE Confidence: 0.9713755 00:12:59.215 --> 00:13:00.255 chance to talk about that NOTE Confidence: 0.9713755 00:13:00.255 --> 00:13:01.695 today, but I think that NOTE Confidence: 0.9713755 00:13:01.695 --> 00:13:03.695 implementation is key. You can NOTE Confidence: 0.9713755 00:13:03.695 --> 00:13:04.655 get all the great drugs NOTE Confidence: 0.9713755 00:13:04.655 --> 00:13:05.535 in the world. You can NOTE Confidence: 0.9713755 00:13:05.535 --> 00:13:06.655 have all these fancy new NOTE Confidence: 0.9713755 00:13:06.655 --> 00:13:08.335 bi diagnostic tests. But if NOTE Confidence: 0.9713755 00:13:08.335 --> 00:13:09.235 patients who NOTE Confidence: 0.8931736 00:13:09.615 --> 00:13:11.075 can have access to a NOTE Confidence: 0.97807413 00:13:11.450 --> 00:13:12.890 basic basically, a fifty dollar NOTE Confidence: 0.97807413 00:13:12.890 --> 00:13:14.730 test can actually learn if NOTE Confidence: 0.97807413 00:13:14.730 --> 00:13:16.170 they might have, a lethal NOTE Confidence: 0.97807413 00:13:16.170 --> 00:13:17.450 cancer, I think that the NOTE Confidence: 0.97807413 00:13:17.450 --> 00:13:18.490 answer is to try to NOTE Confidence: 0.97807413 00:13:18.490 --> 00:13:19.550 to find those patients. NOTE Confidence: 0.9858877 00:13:20.890 --> 00:13:22.250 Okay. So we're gonna switch NOTE Confidence: 0.9858877 00:13:22.250 --> 00:13:24.170 to, more advanced disease. And, NOTE Confidence: 0.9858877 00:13:24.170 --> 00:13:25.130 of course, this is the NOTE Confidence: 0.9858877 00:13:25.130 --> 00:13:26.750 other way in which patients NOTE Confidence: 0.9746536 00:13:27.075 --> 00:13:28.515 progress and unfortunately die of NOTE Confidence: 0.9746536 00:13:28.515 --> 00:13:29.395 the disease. And I'm gonna NOTE Confidence: 0.9746536 00:13:29.395 --> 00:13:30.995 first talk about androgen receptor NOTE Confidence: 0.9746536 00:13:30.995 --> 00:13:32.755 pathway inhibitors, what I call NOTE Confidence: 0.9746536 00:13:32.755 --> 00:13:33.875 the first targeted therapy. You NOTE Confidence: 0.9746536 00:13:33.875 --> 00:13:35.075 know, we talk about targeted NOTE Confidence: 0.9746536 00:13:35.075 --> 00:13:36.275 therapy now. We have all NOTE Confidence: 0.9746536 00:13:36.275 --> 00:13:37.015 these fancy, NOTE Confidence: 0.96031207 00:13:37.635 --> 00:13:39.655 biomarkers. But in truth, androgen NOTE Confidence: 0.96031207 00:13:39.715 --> 00:13:40.215 receptor NOTE Confidence: 0.9875076 00:13:41.120 --> 00:13:42.079 is one of the key NOTE Confidence: 0.9875076 00:13:42.079 --> 00:13:42.480 first, NOTE Confidence: 0.96461713 00:13:42.959 --> 00:13:43.459 pathways. NOTE Confidence: 0.9959812 00:13:43.839 --> 00:13:44.720 And you can see here NOTE Confidence: 0.9959812 00:13:44.720 --> 00:13:45.220 that, NOTE Confidence: 0.98349124 00:13:45.600 --> 00:13:47.059 in pink are four, NOTE Confidence: 0.94820046 00:13:47.519 --> 00:13:48.559 what we call ARPs or NOTE Confidence: 0.94820046 00:13:48.559 --> 00:13:50.399 androgen receptor pathway inhibitors that NOTE Confidence: 0.94820046 00:13:50.399 --> 00:13:52.000 are proven to improve survival NOTE Confidence: 0.94820046 00:13:52.000 --> 00:13:53.699 in multiple disease states within NOTE Confidence: 0.94820046 00:13:53.759 --> 00:13:55.360 the treatment landscape of prostate NOTE Confidence: 0.94820046 00:13:55.360 --> 00:13:55.860 cancer. NOTE Confidence: 0.9763691 00:13:56.865 --> 00:13:58.304 But this history goes back NOTE Confidence: 0.9763691 00:13:58.304 --> 00:13:59.105 many years. In fact, there NOTE Confidence: 0.9763691 00:13:59.105 --> 00:13:59.825 have been at least two NOTE Confidence: 0.9763691 00:13:59.825 --> 00:14:01.585 Nobel prizes awarded for the NOTE Confidence: 0.9763691 00:14:01.585 --> 00:14:03.105 discovery that androgen was a NOTE Confidence: 0.9763691 00:14:03.105 --> 00:14:04.785 driver of prostate cancer. Now NOTE Confidence: 0.9763691 00:14:04.785 --> 00:14:06.145 in twenty twenty five, we NOTE Confidence: 0.9763691 00:14:06.145 --> 00:14:07.605 think it's obvious that androgen NOTE Confidence: 0.9763691 00:14:07.665 --> 00:14:09.425 drives prostate cancer. But back NOTE Confidence: 0.9763691 00:14:09.425 --> 00:14:11.045 when, doctor Huggins NOTE Confidence: 0.9961234 00:14:11.429 --> 00:14:12.570 first did orchiectomies, NOTE Confidence: 0.98934466 00:14:13.190 --> 00:14:14.870 in patients with metastatic prostate NOTE Confidence: 0.98934466 00:14:14.870 --> 00:14:16.090 cancer, it was not obvious NOTE Confidence: 0.98934466 00:14:16.309 --> 00:14:17.670 that prostate cancer was driven NOTE Confidence: 0.98934466 00:14:17.670 --> 00:14:19.770 by testosterone and and androgen NOTE Confidence: 0.98934466 00:14:19.830 --> 00:14:20.330 receptor. NOTE Confidence: 0.97857165 00:14:20.710 --> 00:14:21.830 And this is a long NOTE Confidence: 0.97857165 00:14:21.830 --> 00:14:22.870 history. The second, NOTE Confidence: 0.95166415 00:14:23.510 --> 00:14:24.550 Nobel Prize, by the way, NOTE Confidence: 0.95166415 00:14:24.550 --> 00:14:26.505 was for the chemical synthesis NOTE Confidence: 0.95166415 00:14:26.505 --> 00:14:27.325 of LHRH. NOTE Confidence: 0.9847934 00:14:27.785 --> 00:14:28.904 And the idea here really NOTE Confidence: 0.9847934 00:14:28.904 --> 00:14:30.185 is that this is a NOTE Confidence: 0.9847934 00:14:30.185 --> 00:14:32.105 big disease for which this NOTE Confidence: 0.9847934 00:14:32.105 --> 00:14:34.105 observation has not only led NOTE Confidence: 0.9847934 00:14:34.105 --> 00:14:35.404 to a long standing NOTE Confidence: 0.92212045 00:14:35.705 --> 00:14:37.065 treatment, which we still use, NOTE Confidence: 0.92212045 00:14:37.065 --> 00:14:38.285 so we don't use orchiectomy NOTE Confidence: 0.9649085 00:14:38.585 --> 00:14:39.840 here in the United States. NOTE Confidence: 0.9649085 00:14:39.840 --> 00:14:41.360 It's still used worldwide as NOTE Confidence: 0.9649085 00:14:41.360 --> 00:14:42.960 a very inexpensive way to NOTE Confidence: 0.9649085 00:14:42.960 --> 00:14:44.320 deprive the cancer of its NOTE Confidence: 0.9649085 00:14:44.320 --> 00:14:46.480 ligand. But LHRH agonists and NOTE Confidence: 0.9649085 00:14:46.480 --> 00:14:48.000 antagonists remain a mainstay of NOTE Confidence: 0.9649085 00:14:48.000 --> 00:14:49.860 treatment, basically, androgen deprivation. NOTE Confidence: 0.9617703 00:14:51.120 --> 00:14:52.400 But what really have we NOTE Confidence: 0.9617703 00:14:52.400 --> 00:14:53.840 learned, when I started in NOTE Confidence: 0.9617703 00:14:53.840 --> 00:14:54.960 this field, we said, you NOTE Confidence: 0.9617703 00:14:54.960 --> 00:14:56.204 know what? We we gave NOTE Confidence: 0.9617703 00:14:56.204 --> 00:14:58.045 the patient luprolide. Their testosterone NOTE Confidence: 0.9617703 00:14:58.045 --> 00:14:59.485 went down. We're done. We've NOTE Confidence: 0.9617703 00:14:59.485 --> 00:15:01.404 maximized it. It turned out NOTE Confidence: 0.9617703 00:15:01.404 --> 00:15:02.764 that we were completely wrong. NOTE Confidence: 0.9617703 00:15:02.764 --> 00:15:03.805 And the reason we were NOTE Confidence: 0.9617703 00:15:03.805 --> 00:15:05.584 completely wrong is that androgen NOTE Confidence: 0.9617703 00:15:05.725 --> 00:15:07.084 continued to be an important NOTE Confidence: 0.9617703 00:15:07.084 --> 00:15:08.384 driver of these cancers. NOTE Confidence: 0.9958394 00:15:08.845 --> 00:15:10.410 And we now know that NOTE Confidence: 0.9958394 00:15:10.410 --> 00:15:11.290 there are at least, NOTE Confidence: 0.9993367 00:15:12.010 --> 00:15:13.790 four drugs in this category NOTE Confidence: 0.9179207 00:15:14.250 --> 00:15:16.410 of ARPII that block the NOTE Confidence: 0.9179207 00:15:16.410 --> 00:15:18.730 continued signaling of an androgen NOTE Confidence: 0.9179207 00:15:18.730 --> 00:15:20.250 in these cancer cells. And NOTE Confidence: 0.9179207 00:15:20.250 --> 00:15:21.870 they are listed here, abiraterone, NOTE Confidence: 0.97555524 00:15:22.515 --> 00:15:24.455 apalutamide, darolutamide, and enzalutamide. NOTE Confidence: 0.9771298 00:15:24.835 --> 00:15:26.055 We also know that chemotherapy NOTE Confidence: 0.9771298 00:15:26.275 --> 00:15:27.635 has an impact when these NOTE Confidence: 0.9771298 00:15:27.635 --> 00:15:29.155 cancers first present. We we've NOTE Confidence: 0.9771298 00:15:29.155 --> 00:15:30.355 known that for a while, NOTE Confidence: 0.9771298 00:15:30.355 --> 00:15:31.315 but in fact, when you NOTE Confidence: 0.9771298 00:15:31.315 --> 00:15:32.695 move it early into the NOTE Confidence: 0.9771298 00:15:32.835 --> 00:15:33.335 presentation NOTE Confidence: 0.97844785 00:15:33.715 --> 00:15:35.769 of metastatic prostate cancer, you NOTE Confidence: 0.97844785 00:15:35.769 --> 00:15:37.790 can target this heterogeneity. Heterogeneity NOTE Confidence: 0.97844785 00:15:38.010 --> 00:15:39.690 implies that these cancer cells NOTE Confidence: 0.97844785 00:15:39.690 --> 00:15:41.610 are not uniform monoclonal like NOTE Confidence: 0.97844785 00:15:41.610 --> 00:15:43.209 some leukemias may be. There NOTE Confidence: 0.97844785 00:15:43.209 --> 00:15:44.570 are these different colored cancer NOTE Confidence: 0.97844785 00:15:44.570 --> 00:15:45.070 cells. NOTE Confidence: 0.9861781 00:15:45.529 --> 00:15:46.490 They're not really colored in NOTE Confidence: 0.9861781 00:15:46.490 --> 00:15:48.170 real life, but, but they NOTE Confidence: 0.9861781 00:15:48.170 --> 00:15:50.110 are driven by different driver NOTE Confidence: 0.9931138 00:15:50.415 --> 00:15:52.675 mutations or abnormalities or sensitivity NOTE Confidence: 0.9931138 00:15:52.735 --> 00:15:53.875 to androgen signaling. NOTE Confidence: 0.9775627 00:15:54.255 --> 00:15:55.295 And if you have a NOTE Confidence: 0.9775627 00:15:55.295 --> 00:15:57.795 better androgen androgen signaling inhibitor, NOTE Confidence: 0.95342714 00:15:58.334 --> 00:15:59.695 or chemotherapy that you can NOTE Confidence: 0.95342714 00:15:59.695 --> 00:16:01.135 actually improve survival in these NOTE Confidence: 0.95342714 00:16:01.135 --> 00:16:01.635 patients. NOTE Confidence: 0.9730137 00:16:02.015 --> 00:16:02.894 And there have now been NOTE Confidence: 0.9730137 00:16:02.894 --> 00:16:04.894 eleven prospective clinical trials. This NOTE Confidence: 0.9730137 00:16:04.894 --> 00:16:05.670 is one of the most NOTE Confidence: 0.9730137 00:16:05.750 --> 00:16:08.089 studied and most effective randomized, NOTE Confidence: 0.9977755 00:16:09.350 --> 00:16:10.950 stories that exist in modern NOTE Confidence: 0.9977755 00:16:10.950 --> 00:16:11.450 oncology. NOTE Confidence: 0.9741112 00:16:11.829 --> 00:16:13.910 Okay? Eleven randomized clinical trials NOTE Confidence: 0.9741112 00:16:13.910 --> 00:16:15.750 that show survival benefit for NOTE Confidence: 0.9741112 00:16:15.750 --> 00:16:17.610 combination therapy in metastatic NOTE Confidence: 0.9792979 00:16:18.055 --> 00:16:19.655 hormone sensitive prostate cancer. So NOTE Confidence: 0.9792979 00:16:19.655 --> 00:16:21.175 we call this HSBC or NOTE Confidence: 0.9792979 00:16:21.175 --> 00:16:23.415 hormone sensitive prostate cancer because NOTE Confidence: 0.9792979 00:16:23.415 --> 00:16:24.295 we know that if we NOTE Confidence: 0.9792979 00:16:24.295 --> 00:16:25.735 actually deprive these patients of NOTE Confidence: 0.9792979 00:16:25.735 --> 00:16:27.095 androgen, as I showed you NOTE Confidence: 0.9792979 00:16:27.095 --> 00:16:28.455 with doctor Huggins, we can NOTE Confidence: 0.9792979 00:16:28.455 --> 00:16:29.995 put these cancers into remission. NOTE Confidence: 0.9792979 00:16:30.135 --> 00:16:31.495 But those patients would recur NOTE Confidence: 0.9792979 00:16:31.495 --> 00:16:32.795 within a year or two. NOTE Confidence: 0.9792979 00:16:32.850 --> 00:16:33.970 But what we've shown with NOTE Confidence: 0.9792979 00:16:33.970 --> 00:16:35.250 all of these clinical trials NOTE Confidence: 0.9792979 00:16:35.250 --> 00:16:36.050 is that if you do NOTE Confidence: 0.9792979 00:16:36.050 --> 00:16:37.649 doublets where you add an NOTE Confidence: 0.9792979 00:16:37.649 --> 00:16:39.990 ARPI to androgen deprivation therapy NOTE Confidence: 0.9792979 00:16:40.209 --> 00:16:41.410 or you do triplets where NOTE Confidence: 0.9792979 00:16:41.410 --> 00:16:42.690 you add an ARPI plus NOTE Confidence: 0.9792979 00:16:42.690 --> 00:16:43.190 chemotherapy, NOTE Confidence: 0.9453917 00:16:43.649 --> 00:16:44.769 that you can actually improve NOTE Confidence: 0.9453917 00:16:44.769 --> 00:16:45.730 survival, and you can see NOTE Confidence: 0.9453917 00:16:45.730 --> 00:16:47.190 the hazard ratios there. NOTE Confidence: 0.9853379 00:16:48.705 --> 00:16:49.825 You can improve survival by NOTE Confidence: 0.9853379 00:16:49.825 --> 00:16:50.785 up to twenty to forty NOTE Confidence: 0.9853379 00:16:50.785 --> 00:16:52.145 percent. And all of these NOTE Confidence: 0.9853379 00:16:52.145 --> 00:16:53.125 studies were positive. NOTE Confidence: 0.98577297 00:16:53.505 --> 00:16:55.025 So the the question is NOTE Confidence: 0.98577297 00:16:55.025 --> 00:16:56.305 not if these drugs work. NOTE Confidence: 0.98577297 00:16:56.305 --> 00:16:57.904 The question is, is there NOTE Confidence: 0.98577297 00:16:57.904 --> 00:16:59.185 an optimal sequence? Is there NOTE Confidence: 0.98577297 00:16:59.185 --> 00:17:00.145 one drug better than the NOTE Confidence: 0.98577297 00:17:00.145 --> 00:17:00.865 other? But we're not gonna NOTE Confidence: 0.98577297 00:17:00.865 --> 00:17:01.825 talk about that. We're gonna NOTE Confidence: 0.98577297 00:17:01.825 --> 00:17:02.790 talk about the fact that NOTE Confidence: 0.98577297 00:17:02.870 --> 00:17:04.309 all of these trials, including NOTE Confidence: 0.98577297 00:17:04.309 --> 00:17:05.270 one that didn't even make NOTE Confidence: 0.98577297 00:17:05.270 --> 00:17:06.570 it to this review article NOTE Confidence: 0.98577297 00:17:06.710 --> 00:17:08.330 and was presented very recently, NOTE Confidence: 0.99911785 00:17:08.790 --> 00:17:10.230 all show that these drugs NOTE Confidence: 0.99911785 00:17:10.230 --> 00:17:11.910 should absolutely be used to NOTE Confidence: 0.99911785 00:17:11.910 --> 00:17:12.809 improve survival. NOTE Confidence: 0.9934365 00:17:13.590 --> 00:17:14.549 So, you know, when I NOTE Confidence: 0.9934365 00:17:14.549 --> 00:17:15.690 give talks to patients, NOTE Confidence: 0.9633452 00:17:16.070 --> 00:17:16.790 you know, I try to NOTE Confidence: 0.9633452 00:17:16.790 --> 00:17:18.415 make the story simple. Right? NOTE Confidence: 0.9633452 00:17:18.415 --> 00:17:20.494 So ADT alone, going back NOTE Confidence: 0.9633452 00:17:20.494 --> 00:17:21.935 to the nineteen forties, androgen NOTE Confidence: 0.9633452 00:17:21.935 --> 00:17:24.015 deprivation alone, therapy alone was NOTE Confidence: 0.9633452 00:17:24.015 --> 00:17:25.155 the standard of care. NOTE Confidence: 0.99552464 00:17:26.415 --> 00:17:27.615 Then in the past few NOTE Confidence: 0.99552464 00:17:27.615 --> 00:17:28.494 years, if you look at NOTE Confidence: 0.99552464 00:17:28.494 --> 00:17:30.494 that graphic, we showed that NOTE Confidence: 0.99552464 00:17:30.494 --> 00:17:30.994 chemotherapy NOTE Confidence: 0.8663807 00:17:31.375 --> 00:17:31.830 plus, NOTE Confidence: 0.9309438 00:17:32.470 --> 00:17:34.149 ADT or an r one NOTE Confidence: 0.9309438 00:17:34.149 --> 00:17:36.570 RP plus, ADT improved survival. NOTE Confidence: 0.9309438 00:17:36.630 --> 00:17:37.990 So two drugs were better NOTE Confidence: 0.9309438 00:17:37.990 --> 00:17:38.730 than one. NOTE Confidence: 0.9944168 00:17:39.990 --> 00:17:41.590 Now the triplets showed that NOTE Confidence: 0.9944168 00:17:41.590 --> 00:17:42.490 if you add, NOTE Confidence: 0.99962527 00:17:43.109 --> 00:17:44.010 a third drug NOTE Confidence: 0.94118536 00:17:44.355 --> 00:17:45.795 together, if you add ADT NOTE Confidence: 0.94118536 00:17:45.795 --> 00:17:47.575 plus docetaxel on either abiraterone NOTE Confidence: 0.968707 00:17:47.875 --> 00:17:49.655 or dalutamide, you improve survival. NOTE Confidence: 0.968707 00:17:49.955 --> 00:17:51.315 So, actually, these two options NOTE Confidence: 0.968707 00:17:51.315 --> 00:17:52.195 should really be off the NOTE Confidence: 0.968707 00:17:52.195 --> 00:17:53.715 table now, and you'd be NOTE Confidence: 0.968707 00:17:53.715 --> 00:17:54.215 surprised. NOTE Confidence: 0.9846366 00:17:54.755 --> 00:17:55.875 A lot of patients, in NOTE Confidence: 0.9846366 00:17:55.875 --> 00:17:56.130 fact, NOTE Confidence: 0.99403197 00:17:56.690 --> 00:17:57.670 do not receive, NOTE Confidence: 0.96035975 00:17:58.210 --> 00:17:59.810 these three options here. And NOTE Confidence: 0.96035975 00:17:59.810 --> 00:18:01.590 these options are widely available, NOTE Confidence: 0.98111635 00:18:01.890 --> 00:18:03.010 and we can talk again NOTE Confidence: 0.98111635 00:18:03.010 --> 00:18:04.450 about why they're not always NOTE Confidence: 0.98111635 00:18:04.450 --> 00:18:05.810 used. But sometimes it's the NOTE Confidence: 0.98111635 00:18:05.810 --> 00:18:07.170 doctors themselves, maybe not in NOTE Confidence: 0.98111635 00:18:07.170 --> 00:18:08.965 academic centers like ours, but NOTE Confidence: 0.98111635 00:18:08.965 --> 00:18:10.005 in the community who may NOTE Confidence: 0.98111635 00:18:10.005 --> 00:18:11.145 or may not appreciate, NOTE Confidence: 0.99767536 00:18:12.165 --> 00:18:13.485 how important these drugs are NOTE Confidence: 0.99767536 00:18:13.485 --> 00:18:14.725 in terms of overall survival. NOTE Confidence: 0.99767536 00:18:14.725 --> 00:18:15.845 If you can live forty NOTE Confidence: 0.99767536 00:18:15.845 --> 00:18:17.525 percent longer with these treatments, NOTE Confidence: 0.99767536 00:18:17.525 --> 00:18:18.565 why wouldn't you give these NOTE Confidence: 0.99767536 00:18:18.565 --> 00:18:19.065 treatments? NOTE Confidence: 0.97537863 00:18:19.845 --> 00:18:21.465 So they've asked that question NOTE Confidence: 0.97537863 00:18:21.525 --> 00:18:23.045 in real world studies, and, NOTE Confidence: 0.98211247 00:18:23.659 --> 00:18:24.779 this includes mostly, NOTE Confidence: 0.97124195 00:18:25.179 --> 00:18:26.700 US studies, but also studies NOTE Confidence: 0.97124195 00:18:26.700 --> 00:18:27.820 from other countries. And you NOTE Confidence: 0.97124195 00:18:27.820 --> 00:18:28.299 can see that, NOTE Confidence: 0.9566826 00:18:30.140 --> 00:18:31.419 adding one of these drugs, NOTE Confidence: 0.9566826 00:18:31.419 --> 00:18:32.779 either Dositax or one of NOTE Confidence: 0.9566826 00:18:32.779 --> 00:18:33.100 these, NOTE Confidence: 0.82711864 00:18:33.659 --> 00:18:34.619 it's called the RC here, NOTE Confidence: 0.82711864 00:18:34.619 --> 00:18:35.679 but I mean ARP, NOTE Confidence: 0.9752967 00:18:36.059 --> 00:18:37.340 the one of these extra NOTE Confidence: 0.9752967 00:18:37.340 --> 00:18:38.445 drugs improve, NOTE Confidence: 0.94382197 00:18:39.164 --> 00:18:40.365 were were more likely to NOTE Confidence: 0.94382197 00:18:40.365 --> 00:18:41.645 be used in white patients, NOTE Confidence: 0.94382197 00:18:41.645 --> 00:18:43.804 younger patients, in academic centers, NOTE Confidence: 0.94382197 00:18:43.804 --> 00:18:45.244 and more likely by oncologists NOTE Confidence: 0.94382197 00:18:45.244 --> 00:18:45.984 and neurologists. NOTE Confidence: 0.9973159 00:18:46.445 --> 00:18:47.164 But if you look at NOTE Confidence: 0.9973159 00:18:47.164 --> 00:18:48.605 this graph that was published, NOTE Confidence: 0.9973159 00:18:48.605 --> 00:18:49.645 it looks like we're doing NOTE Confidence: 0.9973159 00:18:49.645 --> 00:18:50.605 pretty well. But if in NOTE Confidence: 0.9973159 00:18:50.605 --> 00:18:51.565 fact, if you actually put NOTE Confidence: 0.9973159 00:18:51.565 --> 00:18:52.765 it on scale, this is NOTE Confidence: 0.9973159 00:18:52.765 --> 00:18:53.940 what it really looks like. NOTE Confidence: 0.9654516 00:18:54.419 --> 00:18:55.539 So we're we're lucky to NOTE Confidence: 0.9654516 00:18:55.539 --> 00:18:57.059 get to fifty percent. At NOTE Confidence: 0.9654516 00:18:57.059 --> 00:18:57.859 at at the time this NOTE Confidence: 0.9654516 00:18:57.859 --> 00:18:58.980 was published, which was just NOTE Confidence: 0.9654516 00:18:58.980 --> 00:19:00.600 last year, it was only, NOTE Confidence: 0.9852666 00:19:01.059 --> 00:19:02.500 it was only about, thirty NOTE Confidence: 0.9852666 00:19:02.500 --> 00:19:03.940 to forty percent were receiving NOTE Confidence: 0.9852666 00:19:03.940 --> 00:19:05.000 a second drug. NOTE Confidence: 0.96380764 00:19:05.460 --> 00:19:07.244 Okay. So this again gets NOTE Confidence: 0.96380764 00:19:07.244 --> 00:19:08.205 to the same point I NOTE Confidence: 0.96380764 00:19:08.205 --> 00:19:09.665 brought up earlier about implementation. NOTE Confidence: 0.9961769 00:19:10.205 --> 00:19:11.005 We can get all these NOTE Confidence: 0.9961769 00:19:11.005 --> 00:19:12.125 great drugs, but if patients NOTE Confidence: 0.9961769 00:19:12.125 --> 00:19:13.165 aren't receiving it, they're not NOTE Confidence: 0.9961769 00:19:13.165 --> 00:19:14.625 getting the survival benefit. NOTE Confidence: 0.9868063 00:19:16.365 --> 00:19:17.565 And I wanna call out, NOTE Confidence: 0.9868063 00:19:17.885 --> 00:19:19.005 that there are other drugs NOTE Confidence: 0.9868063 00:19:19.005 --> 00:19:20.525 coming down this pike, including NOTE Confidence: 0.9868063 00:19:20.525 --> 00:19:20.940 work NOTE Confidence: 0.9605208 00:19:21.340 --> 00:19:22.619 developed here at Yale by NOTE Confidence: 0.9605208 00:19:22.619 --> 00:19:23.980 Craig Cruz, the concept of NOTE Confidence: 0.9605208 00:19:23.980 --> 00:19:24.480 PROTACs, NOTE Confidence: 0.9457755 00:19:25.019 --> 00:19:26.460 AR degraders, and led by NOTE Confidence: 0.9457755 00:19:26.460 --> 00:19:27.820 Dan Petrelac in the original NOTE Confidence: 0.9457755 00:19:27.820 --> 00:19:29.340 clinical trials. And this was NOTE Confidence: 0.9457755 00:19:29.340 --> 00:19:30.700 pub presented last year at NOTE Confidence: 0.9457755 00:19:30.700 --> 00:19:31.659 ASCO, and you can see NOTE Confidence: 0.9457755 00:19:31.659 --> 00:19:32.320 that this, NOTE Confidence: 0.95240575 00:19:32.700 --> 00:19:34.639 PROTAC that degrades AR, NOTE Confidence: 0.9815187 00:19:35.054 --> 00:19:36.335 specifically in patients who have, NOTE Confidence: 0.9815187 00:19:36.734 --> 00:19:38.494 mutations in the ligand binding NOTE Confidence: 0.9815187 00:19:38.494 --> 00:19:39.695 domain, it's beyond the scope NOTE Confidence: 0.9815187 00:19:39.695 --> 00:19:41.054 of this discussion. But these NOTE Confidence: 0.9815187 00:19:41.054 --> 00:19:42.095 are patients who do not NOTE Confidence: 0.9815187 00:19:42.095 --> 00:19:43.234 respond to the current, NOTE Confidence: 0.96441925 00:19:43.855 --> 00:19:45.615 AR, PIs that we have NOTE Confidence: 0.96441925 00:19:45.615 --> 00:19:46.654 at this time. And you NOTE Confidence: 0.96441925 00:19:46.654 --> 00:19:48.254 can see these waterfall plots, NOTE Confidence: 0.96441925 00:19:48.254 --> 00:19:49.554 you see quite a dramatic NOTE Confidence: 0.9731155 00:19:51.000 --> 00:19:52.280 benefit to the use of NOTE Confidence: 0.9731155 00:19:52.280 --> 00:19:53.880 a degrader. So we're gonna NOTE Confidence: 0.9731155 00:19:53.880 --> 00:19:55.740 continue to see androgen signaling NOTE Confidence: 0.9628272 00:19:56.119 --> 00:19:57.720 as an important target for NOTE Confidence: 0.9628272 00:19:57.720 --> 00:19:59.900 anticancer therapy and prostate cancer. NOTE Confidence: 0.95382553 00:20:00.440 --> 00:20:01.960 So here's a a story NOTE Confidence: 0.95382553 00:20:01.960 --> 00:20:03.800 that has evolved over not NOTE Confidence: 0.95382553 00:20:03.800 --> 00:20:05.080 just a few decades, but NOTE Confidence: 0.95382553 00:20:05.080 --> 00:20:05.580 over NOTE Confidence: 0.9792357 00:20:05.905 --> 00:20:07.445 almost a century. We're coming, NOTE Confidence: 0.9792357 00:20:07.585 --> 00:20:08.565 you know, in the next NOTE Confidence: 0.9792357 00:20:08.705 --> 00:20:10.145 sixty, seventy, eighty years we've NOTE Confidence: 0.9792357 00:20:10.145 --> 00:20:11.605 been using these treatments. But, NOTE Confidence: 0.9792357 00:20:11.825 --> 00:20:12.945 we think we're done, but NOTE Confidence: 0.9792357 00:20:12.945 --> 00:20:13.905 we keep getting better and NOTE Confidence: 0.9792357 00:20:13.905 --> 00:20:14.785 better, and you're gonna see NOTE Confidence: 0.9792357 00:20:14.785 --> 00:20:15.665 more of these drugs in NOTE Confidence: 0.9792357 00:20:15.665 --> 00:20:16.405 that setting. NOTE Confidence: 0.9993105 00:20:17.585 --> 00:20:18.625 Okay. So how else can NOTE Confidence: 0.9993105 00:20:18.625 --> 00:20:19.445 we be better? NOTE Confidence: 0.9974321 00:20:20.420 --> 00:20:21.859 You know, biomarkers are a NOTE Confidence: 0.9974321 00:20:21.859 --> 00:20:23.220 hot topic. People talk about NOTE Confidence: 0.9974321 00:20:23.220 --> 00:20:24.260 it all the time. That NOTE Confidence: 0.9974321 00:20:24.260 --> 00:20:25.780 is the key to doing NOTE Confidence: 0.9974321 00:20:25.780 --> 00:20:27.859 better precision medicine. Right? So NOTE Confidence: 0.9974321 00:20:27.859 --> 00:20:28.660 I'm gonna talk a little NOTE Confidence: 0.9974321 00:20:28.660 --> 00:20:29.780 bit about the story here NOTE Confidence: 0.9974321 00:20:29.780 --> 00:20:31.059 in prostate cancer with regard NOTE Confidence: 0.9974321 00:20:31.059 --> 00:20:33.059 to both molecular biomarkers and NOTE Confidence: 0.9974321 00:20:33.059 --> 00:20:34.520 PARP inhibitors in particular. NOTE Confidence: 0.94111985 00:20:36.255 --> 00:20:38.335 So, in this graphic, there's NOTE Confidence: 0.94111985 00:20:38.335 --> 00:20:39.855 two areas that a biomarker NOTE Confidence: 0.94111985 00:20:39.935 --> 00:20:41.615 that are biomarker driven, PARP NOTE Confidence: 0.94111985 00:20:41.615 --> 00:20:42.994 inhibitors and pembrolizumab. NOTE Confidence: 0.9239735 00:20:43.455 --> 00:20:44.575 And I'll just talk briefly NOTE Confidence: 0.9239735 00:20:44.575 --> 00:20:45.315 about both. NOTE Confidence: 0.99753714 00:20:45.695 --> 00:20:46.895 But this is an article NOTE Confidence: 0.99753714 00:20:46.895 --> 00:20:48.355 from a few years ago NOTE Confidence: 0.99825996 00:20:49.350 --> 00:20:51.190 that really shows the FDA NOTE Confidence: 0.99825996 00:20:51.190 --> 00:20:51.690 approvals, NOTE Confidence: 0.98301965 00:20:52.230 --> 00:20:54.070 over the last twenty years NOTE Confidence: 0.98301965 00:20:54.070 --> 00:20:55.109 and how many of them NOTE Confidence: 0.98301965 00:20:55.109 --> 00:20:56.630 are really biomarker driven. You NOTE Confidence: 0.98301965 00:20:56.630 --> 00:20:57.910 can see that the blue NOTE Confidence: 0.98301965 00:20:57.910 --> 00:20:59.530 are biomarker driven approvals. NOTE Confidence: 0.9773381 00:20:59.910 --> 00:21:01.190 And I couldn't find a NOTE Confidence: 0.9773381 00:21:01.190 --> 00:21:02.630 more recent updated version, but NOTE Confidence: 0.9773381 00:21:02.630 --> 00:21:04.230 it's probably continued and even NOTE Confidence: 0.9773381 00:21:04.230 --> 00:21:05.565 more so. And you can NOTE Confidence: 0.9773381 00:21:05.565 --> 00:21:06.605 see that in in recent NOTE Confidence: 0.9773381 00:21:06.605 --> 00:21:07.645 years, at least half of NOTE Confidence: 0.9773381 00:21:07.645 --> 00:21:09.404 all drug approvals by the NOTE Confidence: 0.9773381 00:21:09.404 --> 00:21:10.465 FDA are actually, NOTE Confidence: 0.98408085 00:21:11.005 --> 00:21:12.524 have an associated biomarker. And NOTE Confidence: 0.98408085 00:21:12.524 --> 00:21:13.484 what this really points out NOTE Confidence: 0.98408085 00:21:13.484 --> 00:21:14.524 is prostate cancer is not NOTE Confidence: 0.98408085 00:21:14.524 --> 00:21:16.205 prostate cancer. Lung cancer, we NOTE Confidence: 0.98408085 00:21:16.205 --> 00:21:17.609 know that's the prototypical story. NOTE Confidence: 0.98408085 00:21:17.609 --> 00:21:19.050 It's not lung cancer. It's NOTE Confidence: 0.98408085 00:21:19.050 --> 00:21:20.890 EGFR mutated lung cancer or NOTE Confidence: 0.98408085 00:21:20.890 --> 00:21:21.390 it's, NOTE Confidence: 0.97886753 00:21:22.250 --> 00:21:22.730 it's, NOTE Confidence: 0.96360564 00:21:23.210 --> 00:21:24.970 ROS fusion lung cancer. And NOTE Confidence: 0.96360564 00:21:24.970 --> 00:21:25.850 the same thing is true NOTE Confidence: 0.96360564 00:21:25.850 --> 00:21:27.690 in prostate cancer except that NOTE Confidence: 0.96360564 00:21:27.690 --> 00:21:29.230 we have fewer clear biomarkers. NOTE Confidence: 0.96360564 00:21:29.369 --> 00:21:30.330 But I just this is NOTE Confidence: 0.96360564 00:21:30.330 --> 00:21:31.950 an interesting paper from, NOTE Confidence: 0.94140303 00:21:32.515 --> 00:21:34.135 also, from last year from, NOTE Confidence: 0.9653808 00:21:35.234 --> 00:21:36.595 from a a a prominent NOTE Confidence: 0.9653808 00:21:36.595 --> 00:21:38.035 group that looked at the NOTE Confidence: 0.9653808 00:21:38.035 --> 00:21:40.195 rates of molecularly driven treatment NOTE Confidence: 0.9653808 00:21:40.195 --> 00:21:42.035 decisions. So this concept of NOTE Confidence: 0.9653808 00:21:42.035 --> 00:21:43.575 targeted precision therapy. NOTE Confidence: 0.96505964 00:21:43.875 --> 00:21:45.095 And we know that, NOTE Confidence: 0.97359246 00:21:46.240 --> 00:21:46.740 precision NOTE Confidence: 0.87440234 00:21:47.679 --> 00:21:48.720 tier one and tier two, NOTE Confidence: 0.87440234 00:21:49.039 --> 00:21:49.539 mutations NOTE Confidence: 0.9881627 00:21:50.240 --> 00:21:50.740 represent NOTE Confidence: 0.93933284 00:21:51.200 --> 00:21:51.700 about, NOTE Confidence: 0.9557955 00:21:52.080 --> 00:21:54.080 in twenty seventeen represented about NOTE Confidence: 0.9557955 00:21:54.080 --> 00:21:55.840 nine percent of all patients NOTE Confidence: 0.9557955 00:21:55.840 --> 00:21:56.340 presenting, NOTE Confidence: 0.91581804 00:21:56.960 --> 00:21:58.580 across the board, all cancers. NOTE Confidence: 0.99829733 00:21:58.905 --> 00:21:59.865 And that went up to NOTE Confidence: 0.99829733 00:21:59.865 --> 00:22:01.625 thirty one point six percent, NOTE Confidence: 0.99829733 00:22:01.865 --> 00:22:02.845 five years later. NOTE Confidence: 0.9454348 00:22:03.225 --> 00:22:05.385 Okay? And similarly, the number NOTE Confidence: 0.9454348 00:22:05.385 --> 00:22:05.625 of, NOTE Confidence: 0.9924433 00:22:06.505 --> 00:22:07.005 undetermined, NOTE Confidence: 0.97982013 00:22:08.025 --> 00:22:09.885 drivers or drivers without actionability NOTE Confidence: 0.97982013 00:22:10.025 --> 00:22:11.405 went down by about half. NOTE Confidence: 0.97982013 00:22:11.520 --> 00:22:13.119 So you might say, depending NOTE Confidence: 0.97982013 00:22:13.119 --> 00:22:14.400 on your, you know, point NOTE Confidence: 0.97982013 00:22:14.400 --> 00:22:15.280 of view in the world, NOTE Confidence: 0.97982013 00:22:15.280 --> 00:22:16.320 are you a half full NOTE Confidence: 0.97982013 00:22:16.320 --> 00:22:17.540 or half empty person? NOTE Confidence: 0.9834286 00:22:18.800 --> 00:22:20.080 Going from nine percent to NOTE Confidence: 0.9834286 00:22:20.080 --> 00:22:21.440 thirty one percent in just NOTE Confidence: 0.9834286 00:22:21.440 --> 00:22:22.900 five years is pretty dramatic, NOTE Confidence: 0.99902153 00:22:23.359 --> 00:22:24.640 but two thirds of patients NOTE Confidence: 0.99902153 00:22:24.640 --> 00:22:26.420 still don't have actionable mutations NOTE Confidence: 0.997191 00:22:26.775 --> 00:22:27.895 if you do sequencing of NOTE Confidence: 0.997191 00:22:27.895 --> 00:22:28.635 their tumors. NOTE Confidence: 0.9649981 00:22:29.015 --> 00:22:30.215 And this actually this paper NOTE Confidence: 0.9649981 00:22:30.215 --> 00:22:31.175 came out of Memorial Sloan NOTE Confidence: 0.9649981 00:22:31.175 --> 00:22:32.695 Kettering. So the question is, NOTE Confidence: 0.9649981 00:22:32.695 --> 00:22:34.315 in the average community practice, NOTE Confidence: 0.9649981 00:22:34.535 --> 00:22:35.335 you know, if they're not NOTE Confidence: 0.9649981 00:22:35.335 --> 00:22:36.455 doing all of the sequencing, NOTE Confidence: 0.9649981 00:22:36.455 --> 00:22:37.975 are they getting the benefit NOTE Confidence: 0.9649981 00:22:37.975 --> 00:22:39.355 of these actionable mutations? NOTE Confidence: 0.99633 00:22:40.550 --> 00:22:41.830 It turns out prostate cancer NOTE Confidence: 0.99633 00:22:41.830 --> 00:22:42.970 is driven by, NOTE Confidence: 0.95981437 00:22:43.590 --> 00:22:46.010 molecular alter alterations, most importantly, NOTE Confidence: 0.95981437 00:22:46.070 --> 00:22:47.609 DNA damage repair mutations NOTE Confidence: 0.9754063 00:22:47.990 --> 00:22:49.429 or DDR mutations. And you NOTE Confidence: 0.9754063 00:22:49.429 --> 00:22:50.309 can see here, if you NOTE Confidence: 0.9754063 00:22:50.309 --> 00:22:51.609 look at the mutations, NOTE Confidence: 0.9455051 00:22:52.309 --> 00:22:53.670 BRCA two is the most NOTE Confidence: 0.9455051 00:22:53.670 --> 00:22:55.555 common one. So this sometimes NOTE Confidence: 0.9455051 00:22:55.555 --> 00:22:57.735 surprises patients because with BRCA, NOTE Confidence: 0.9455051 00:22:57.875 --> 00:22:59.075 of course, BRCA was named NOTE Confidence: 0.9455051 00:22:59.075 --> 00:23:00.675 after breast cancer, but this NOTE Confidence: 0.9455051 00:23:00.675 --> 00:23:02.755 gene in prostate cancer patients NOTE Confidence: 0.9455051 00:23:02.755 --> 00:23:04.135 is associated with, NOTE Confidence: 0.979558 00:23:04.675 --> 00:23:06.675 both a worse prognosis, earlier NOTE Confidence: 0.979558 00:23:06.675 --> 00:23:07.175 diagnosis, NOTE Confidence: 0.984096 00:23:07.475 --> 00:23:08.695 but also significant, NOTE Confidence: 0.8640049 00:23:11.390 --> 00:23:12.450 significantly worse outcomes. NOTE Confidence: 0.9651392 00:23:13.070 --> 00:23:14.109 And and if you look NOTE Confidence: 0.9651392 00:23:14.109 --> 00:23:15.550 at these, about a quarter NOTE Confidence: 0.9651392 00:23:15.550 --> 00:23:17.070 of patients with advanced prostate NOTE Confidence: 0.9651392 00:23:17.070 --> 00:23:19.230 cancer or CRPC, castration resistant NOTE Confidence: 0.9651392 00:23:19.230 --> 00:23:20.130 prostate cancer, NOTE Confidence: 0.9900743 00:23:20.430 --> 00:23:20.930 have, NOTE Confidence: 0.99809974 00:23:21.390 --> 00:23:22.590 a mutation in in one NOTE Confidence: 0.99809974 00:23:22.590 --> 00:23:23.950 of these DNA damage repair NOTE Confidence: 0.99809974 00:23:23.950 --> 00:23:24.450 mutations. NOTE Confidence: 0.98828673 00:23:25.585 --> 00:23:26.785 Fifty percent of those are NOTE Confidence: 0.98828673 00:23:26.785 --> 00:23:28.225 germline, meaning they inherited it NOTE Confidence: 0.98828673 00:23:28.225 --> 00:23:29.105 from their mother or father, NOTE Confidence: 0.98828673 00:23:29.105 --> 00:23:31.265 and fifty percent are, somatic, NOTE Confidence: 0.98828673 00:23:31.265 --> 00:23:32.945 meaning they developed it, during NOTE Confidence: 0.98828673 00:23:32.945 --> 00:23:33.605 their lifetime. NOTE Confidence: 0.96476775 00:23:34.305 --> 00:23:35.265 One of the things that NOTE Confidence: 0.96476775 00:23:35.265 --> 00:23:36.885 we've learned certainly from preclinical NOTE Confidence: 0.96476775 00:23:36.945 --> 00:23:38.545 work is that there probably NOTE Confidence: 0.96476775 00:23:38.545 --> 00:23:40.545 is a synergy between androgen NOTE Confidence: 0.96476775 00:23:40.545 --> 00:23:42.299 signaling and and blocking androgen NOTE Confidence: 0.96476775 00:23:42.299 --> 00:23:42.799 signaling NOTE Confidence: 0.95544046 00:23:43.100 --> 00:23:43.600 and, NOTE Confidence: 0.9913334 00:23:43.980 --> 00:23:45.500 and these DNA damage repair NOTE Confidence: 0.9913334 00:23:45.500 --> 00:23:46.000 mutations. NOTE Confidence: 0.9845103 00:23:47.340 --> 00:23:48.859 And, and so the the NOTE Confidence: 0.9845103 00:23:48.859 --> 00:23:50.640 the hypothesis based on preclinical NOTE Confidence: 0.9845103 00:23:50.779 --> 00:23:52.240 work was that combining NOTE Confidence: 0.9684274 00:23:52.700 --> 00:23:54.375 an ARP with a PARP NOTE Confidence: 0.9684274 00:23:54.375 --> 00:23:56.615 inhibitor would actually improve outcomes NOTE Confidence: 0.9684274 00:23:56.615 --> 00:23:58.155 in patients with prostate cancer. NOTE Confidence: 0.9347372 00:23:58.695 --> 00:24:00.775 So two trials three trials NOTE Confidence: 0.9347372 00:24:00.775 --> 00:24:02.535 recently about a year ago, NOTE Confidence: 0.9347372 00:24:02.535 --> 00:24:03.815 actually, a few years ago, NOTE Confidence: 0.9347372 00:24:03.815 --> 00:24:04.955 have shown that, NOTE Confidence: 0.945134 00:24:05.415 --> 00:24:06.615 survival is improved if you NOTE Confidence: 0.945134 00:24:06.615 --> 00:24:08.475 actually combine a PARP inhibitor NOTE Confidence: 0.945134 00:24:08.535 --> 00:24:08.775 with, NOTE Confidence: 0.97189033 00:24:09.359 --> 00:24:10.720 one of these androgen receptor NOTE Confidence: 0.97189033 00:24:10.720 --> 00:24:11.840 pathway inhibitors. And this is NOTE Confidence: 0.97189033 00:24:11.840 --> 00:24:13.220 one of the studies, PROPEL, NOTE Confidence: 0.97189033 00:24:13.359 --> 00:24:15.140 which combined olaparib with abiraterone NOTE Confidence: 0.9510712 00:24:15.600 --> 00:24:16.820 versus, placebo, NOTE Confidence: 0.99748254 00:24:17.280 --> 00:24:18.100 plus abiraterone. NOTE Confidence: 0.93297327 00:24:18.800 --> 00:24:20.160 And you can see that NOTE Confidence: 0.93297327 00:24:20.160 --> 00:24:21.840 particularly in the BRCA sub NOTE Confidence: 0.93297327 00:24:21.920 --> 00:24:23.859 mutated subset, a very significant NOTE Confidence: 0.93297327 00:24:24.080 --> 00:24:25.315 improvement, in this case in NOTE Confidence: 0.93297327 00:24:25.315 --> 00:24:26.135 overall survival. NOTE Confidence: 0.9664426 00:24:26.515 --> 00:24:27.234 So we know that if NOTE Confidence: 0.9664426 00:24:27.234 --> 00:24:28.115 you carry one of these NOTE Confidence: 0.9664426 00:24:28.115 --> 00:24:29.635 mutations, you should be getting NOTE Confidence: 0.9664426 00:24:29.635 --> 00:24:30.915 a PARP inhibitor. But more NOTE Confidence: 0.9664426 00:24:30.915 --> 00:24:31.875 importantly, you should be getting NOTE Confidence: 0.9664426 00:24:31.875 --> 00:24:32.835 it right up front. You NOTE Confidence: 0.9664426 00:24:32.835 --> 00:24:34.515 shouldn't be getting it later. NOTE Confidence: 0.9664426 00:24:34.515 --> 00:24:36.315 This this drug was approved, NOTE Confidence: 0.959693 00:24:36.755 --> 00:24:37.635 quite a number of years NOTE Confidence: 0.959693 00:24:37.635 --> 00:24:39.315 ago if you progressed after NOTE Confidence: 0.959693 00:24:39.315 --> 00:24:40.375 a drug like abiraterone. NOTE Confidence: 0.96205455 00:24:40.890 --> 00:24:42.170 But now this these studies NOTE Confidence: 0.96205455 00:24:42.170 --> 00:24:43.130 seem to suggest that you NOTE Confidence: 0.96205455 00:24:43.130 --> 00:24:44.010 should be getting them right NOTE Confidence: 0.96205455 00:24:44.010 --> 00:24:44.890 up front, right at the NOTE Confidence: 0.96205455 00:24:44.890 --> 00:24:46.350 time of metastatic disease. NOTE Confidence: 0.9434669 00:24:47.130 --> 00:24:48.250 And the second study that NOTE Confidence: 0.9434669 00:24:48.250 --> 00:24:49.290 is really in flight right NOTE Confidence: 0.9434669 00:24:49.290 --> 00:24:51.070 at this moment is Talopro NOTE Confidence: 0.9434669 00:24:51.210 --> 00:24:52.890 two. Again, a a different NOTE Confidence: 0.9434669 00:24:52.890 --> 00:24:54.350 PARP inhibitor called talazoparib, NOTE Confidence: 0.9745585 00:24:55.255 --> 00:24:57.255 combined with enzalutamide versus placebo NOTE Confidence: 0.9745585 00:24:57.255 --> 00:24:58.695 plus enzalutamide. Again, a very NOTE Confidence: 0.9745585 00:24:58.695 --> 00:25:00.554 similar endpoint, which is, radiographic NOTE Confidence: 0.9745585 00:25:00.695 --> 00:25:02.294 progression free survival. And you NOTE Confidence: 0.9745585 00:25:02.294 --> 00:25:03.335 can see that in all NOTE Confidence: 0.9745585 00:25:03.335 --> 00:25:04.794 patients, there is a benefit NOTE Confidence: 0.9854158 00:25:05.335 --> 00:25:05.835 to, NOTE Confidence: 0.98443335 00:25:06.455 --> 00:25:07.275 to the combo, NOTE Confidence: 0.9787059 00:25:08.190 --> 00:25:08.590 but, NOTE Confidence: 0.9743526 00:25:09.230 --> 00:25:11.549 more significant in HRR or, NOTE Confidence: 0.9743526 00:25:11.789 --> 00:25:13.250 DDR deficient tumors. NOTE Confidence: 0.98884857 00:25:13.789 --> 00:25:14.590 They did put out a NOTE Confidence: 0.98884857 00:25:14.590 --> 00:25:16.029 press release that suggests that NOTE Confidence: 0.98884857 00:25:16.029 --> 00:25:18.029 maybe this, this combination works NOTE Confidence: 0.98884857 00:25:18.029 --> 00:25:19.390 in all comers. I think NOTE Confidence: 0.98884857 00:25:19.390 --> 00:25:20.190 we have to wait and NOTE Confidence: 0.98884857 00:25:20.190 --> 00:25:21.549 see, when that data is NOTE Confidence: 0.98884857 00:25:21.549 --> 00:25:22.049 presented. NOTE Confidence: 0.94197685 00:25:22.705 --> 00:25:23.985 So the FDA has now NOTE Confidence: 0.94197685 00:25:23.985 --> 00:25:24.485 approved, NOTE Confidence: 0.9956955 00:25:25.025 --> 00:25:26.385 at least three combinations that NOTE Confidence: 0.9956955 00:25:26.385 --> 00:25:27.345 are listed here. I didn't NOTE Confidence: 0.9956955 00:25:27.345 --> 00:25:28.305 show you the third study NOTE Confidence: 0.9956955 00:25:28.305 --> 00:25:28.965 of niraparib. NOTE Confidence: 0.95428985 00:25:29.585 --> 00:25:30.865 But what does this mean? NOTE Confidence: 0.95428985 00:25:30.865 --> 00:25:32.385 This means that in patients NOTE Confidence: 0.95428985 00:25:32.385 --> 00:25:33.825 certainly with a DNA damage NOTE Confidence: 0.95428985 00:25:33.825 --> 00:25:34.725 repair mutation, NOTE Confidence: 0.9246987 00:25:35.185 --> 00:25:37.045 most important one being BRCA NOTE Confidence: 0.9246987 00:25:37.185 --> 00:25:38.460 one or two, that that NOTE Confidence: 0.9246987 00:25:38.460 --> 00:25:39.740 these patients should receive a NOTE Confidence: 0.9246987 00:25:39.740 --> 00:25:41.740 combination of an ARP plus NOTE Confidence: 0.9246987 00:25:41.740 --> 00:25:42.640 a PARP inhibitor. NOTE Confidence: 0.99854547 00:25:43.820 --> 00:25:45.020 But similar to the story NOTE Confidence: 0.99854547 00:25:45.020 --> 00:25:46.240 I've been telling you before, NOTE Confidence: 0.9653735 00:25:46.700 --> 00:25:48.140 people don't get tested. It NOTE Confidence: 0.9653735 00:25:48.140 --> 00:25:49.179 is, this is a real NOTE Confidence: 0.9653735 00:25:49.179 --> 00:25:50.780 world evidence study actually from NOTE Confidence: 0.9653735 00:25:50.780 --> 00:25:52.275 the Flatiron Group that shows NOTE Confidence: 0.9653735 00:25:52.275 --> 00:25:53.555 that about sixty percent of NOTE Confidence: 0.9653735 00:25:53.555 --> 00:25:55.255 patients never get tested NOTE Confidence: 0.9993274 00:25:55.555 --> 00:25:56.455 for these mutations. NOTE Confidence: 0.979575 00:25:56.994 --> 00:25:58.355 So as of now, in NOTE Confidence: 0.979575 00:25:58.355 --> 00:25:59.395 order to be a candidate, NOTE Confidence: 0.979575 00:25:59.395 --> 00:26:00.275 you have to be tested. NOTE Confidence: 0.979575 00:26:00.275 --> 00:26:01.075 And you can see that NOTE Confidence: 0.979575 00:26:01.075 --> 00:26:01.875 there was a little bit NOTE Confidence: 0.979575 00:26:01.875 --> 00:26:03.395 of a blip down during NOTE Confidence: 0.979575 00:26:03.395 --> 00:26:05.429 COVID. But in general, about NOTE Confidence: 0.979575 00:26:05.429 --> 00:26:06.790 six only about forty percent NOTE Confidence: 0.979575 00:26:06.790 --> 00:26:08.309 of patients nationally get tested NOTE Confidence: 0.979575 00:26:08.309 --> 00:26:10.010 for DNA damage repair mutations. NOTE Confidence: 0.979575 00:26:10.309 --> 00:26:11.030 So you if you don't NOTE Confidence: 0.979575 00:26:11.030 --> 00:26:12.070 get tested, you'll never be NOTE Confidence: 0.979575 00:26:12.070 --> 00:26:13.030 able to benefit from the NOTE Confidence: 0.979575 00:26:13.030 --> 00:26:13.530 treatment. NOTE Confidence: 0.99858284 00:26:15.270 --> 00:26:15.770 Okay. NOTE Confidence: 0.98554295 00:26:16.635 --> 00:26:17.835 I think, if we haven't NOTE Confidence: 0.98554295 00:26:17.835 --> 00:26:19.855 had a PSMA PET talk NOTE Confidence: 0.98554295 00:26:19.915 --> 00:26:21.515 in for this group, I NOTE Confidence: 0.98554295 00:26:21.515 --> 00:26:22.555 I hope we do have NOTE Confidence: 0.98554295 00:26:22.555 --> 00:26:24.155 one soon because it's completely NOTE Confidence: 0.98554295 00:26:24.155 --> 00:26:24.655 transformed NOTE Confidence: 0.999187 00:26:25.275 --> 00:26:26.395 the way we treat these NOTE Confidence: 0.999187 00:26:26.395 --> 00:26:27.515 patients. I've been taking care NOTE Confidence: 0.999187 00:26:27.515 --> 00:26:28.795 of prostate cancer for twenty NOTE Confidence: 0.999187 00:26:28.795 --> 00:26:30.715 five years. PSMA PET has NOTE Confidence: 0.999187 00:26:30.715 --> 00:26:31.215 completely NOTE Confidence: 0.9531023 00:26:31.690 --> 00:26:33.070 changed the way we visualize NOTE Confidence: 0.9531023 00:26:33.130 --> 00:26:34.730 prostate cancer. Now this is NOTE Confidence: 0.9531023 00:26:34.730 --> 00:26:36.010 a clinical states model that NOTE Confidence: 0.9531023 00:26:36.010 --> 00:26:37.690 I've shown many years now. NOTE Confidence: 0.9531023 00:26:37.690 --> 00:26:38.730 If you start present with NOTE Confidence: 0.9531023 00:26:38.730 --> 00:26:41.050 clinically localized prostate cancer, you NOTE Confidence: 0.9531023 00:26:41.050 --> 00:26:43.210 have, radical prostatectomy by doctor NOTE Confidence: 0.9531023 00:26:43.210 --> 00:26:44.650 Kim and you you're cured NOTE Confidence: 0.9531023 00:26:44.650 --> 00:26:45.850 or you get radiation and NOTE Confidence: 0.9531023 00:26:45.850 --> 00:26:47.195 you're cured. But if you NOTE Confidence: 0.9531023 00:26:47.195 --> 00:26:48.315 aren't and at least a NOTE Confidence: 0.9531023 00:26:48.315 --> 00:26:49.355 third of patients are not NOTE Confidence: 0.9531023 00:26:49.355 --> 00:26:49.855 cured, NOTE Confidence: 0.9827884 00:26:50.155 --> 00:26:51.355 they go through these disease NOTE Confidence: 0.9827884 00:26:51.355 --> 00:26:52.475 states going from left to NOTE Confidence: 0.9827884 00:26:52.475 --> 00:26:53.295 right where, NOTE Confidence: 0.97925055 00:26:53.675 --> 00:26:54.555 where you might have a NOTE Confidence: 0.97925055 00:26:54.555 --> 00:26:55.994 rising PSA and then you NOTE Confidence: 0.97925055 00:26:55.994 --> 00:26:57.515 develop metastatic disease like I NOTE Confidence: 0.97925055 00:26:57.515 --> 00:26:58.635 talked about earlier, which is NOTE Confidence: 0.97925055 00:26:58.635 --> 00:27:00.075 on the bottom there. At NOTE Confidence: 0.97925055 00:27:00.075 --> 00:27:01.359 the top, though, there's this NOTE Confidence: 0.97925055 00:27:01.359 --> 00:27:02.880 interesting state that we defined NOTE Confidence: 0.97925055 00:27:02.880 --> 00:27:03.619 as nonmetastatic NOTE Confidence: 0.9518594 00:27:04.240 --> 00:27:05.600 but hormone sensitive and then NOTE Confidence: 0.9518594 00:27:05.600 --> 00:27:06.880 castration resistant. What does that NOTE Confidence: 0.9518594 00:27:06.880 --> 00:27:07.619 mean nonmetastatic? NOTE Confidence: 0.98352695 00:27:08.080 --> 00:27:08.880 Well, it doesn't mean that NOTE Confidence: 0.98352695 00:27:08.880 --> 00:27:09.919 they don't have metastasis. It NOTE Confidence: 0.98352695 00:27:09.919 --> 00:27:10.720 means that we can't see NOTE Confidence: 0.98352695 00:27:10.720 --> 00:27:12.559 it with traditional scans like NOTE Confidence: 0.98352695 00:27:12.559 --> 00:27:13.945 bone scan and CAT scan. NOTE Confidence: 0.98352695 00:27:13.945 --> 00:27:15.065 That's really what it means. NOTE Confidence: 0.98352695 00:27:15.065 --> 00:27:16.285 It means that our imaging NOTE Confidence: 0.99979657 00:27:16.825 --> 00:27:18.285 was not able to detect NOTE Confidence: 0.9933126 00:27:18.665 --> 00:27:19.945 what we knew that was, NOTE Confidence: 0.9933126 00:27:20.185 --> 00:27:21.545 cancer progressing. How do we NOTE Confidence: 0.9933126 00:27:21.545 --> 00:27:22.665 know that their cancers were NOTE Confidence: 0.9933126 00:27:22.665 --> 00:27:23.865 progressing? Well, we have a NOTE Confidence: 0.9933126 00:27:23.865 --> 00:27:25.305 biomarker that I started this NOTE Confidence: 0.9933126 00:27:25.305 --> 00:27:26.765 whole conversation with PSA NOTE Confidence: 0.9799366 00:27:27.145 --> 00:27:28.345 that even though it's very NOTE Confidence: 0.9799366 00:27:28.345 --> 00:27:29.970 controversial as a as a NOTE Confidence: 0.9799366 00:27:29.970 --> 00:27:30.470 biomarker NOTE Confidence: 0.98942673 00:27:30.770 --> 00:27:31.270 for, NOTE Confidence: 0.99891347 00:27:32.690 --> 00:27:34.130 for screening, it is not NOTE Confidence: 0.99891347 00:27:34.130 --> 00:27:35.570 controversial at all as a NOTE Confidence: 0.99891347 00:27:35.570 --> 00:27:36.710 biomarker for monitoring. NOTE Confidence: 0.9888671 00:27:37.090 --> 00:27:38.290 We use it all the NOTE Confidence: 0.9888671 00:27:38.290 --> 00:27:39.730 time to monitor whether patients NOTE Confidence: 0.9888671 00:27:39.730 --> 00:27:41.330 are progressing or not. So NOTE Confidence: 0.9888671 00:27:41.330 --> 00:27:42.554 as I said, we've actually NOTE Confidence: 0.9888671 00:27:42.554 --> 00:27:43.674 gone through this state where NOTE Confidence: 0.9888671 00:27:43.674 --> 00:27:44.955 we actually used to use NOTE Confidence: 0.9888671 00:27:44.955 --> 00:27:46.394 bone scan and CT scan, NOTE Confidence: 0.9888671 00:27:46.394 --> 00:27:47.835 but we've completely shifted to NOTE Confidence: 0.9888671 00:27:47.835 --> 00:27:49.115 the use of PET scan NOTE Confidence: 0.9888671 00:27:49.115 --> 00:27:49.934 with CT. NOTE Confidence: 0.9522613 00:27:50.475 --> 00:27:51.674 Why? I at least I NOTE Confidence: 0.9522613 00:27:51.674 --> 00:27:52.475 have. I was on a NOTE Confidence: 0.9522613 00:27:52.475 --> 00:27:53.914 panel. I was sitting there, NOTE Confidence: 0.9522613 00:27:53.914 --> 00:27:54.794 and I said, I don't NOTE Confidence: 0.9522613 00:27:54.794 --> 00:27:56.575 do bone scans anymore. And, NOTE Confidence: 0.98143893 00:27:57.190 --> 00:27:58.450 you know, prominent urologist, NOTE Confidence: 0.97479737 00:27:58.990 --> 00:28:00.270 you know, kind of tried NOTE Confidence: 0.97479737 00:28:00.270 --> 00:28:01.150 to berate me for it. NOTE Confidence: 0.97479737 00:28:01.150 --> 00:28:02.510 But in truth, if I'm NOTE Confidence: 0.97479737 00:28:02.510 --> 00:28:03.550 able to get a PSMA NOTE Confidence: 0.97479737 00:28:03.550 --> 00:28:05.230 PET scan, it is far NOTE Confidence: 0.97479737 00:28:05.230 --> 00:28:06.750 superior to what information I NOTE Confidence: 0.97479737 00:28:06.750 --> 00:28:07.630 might get from a bone NOTE Confidence: 0.97479737 00:28:07.630 --> 00:28:08.130 scan. NOTE Confidence: 0.9759838 00:28:08.670 --> 00:28:10.770 Now PSMA is an interesting, NOTE Confidence: 0.9901895 00:28:11.365 --> 00:28:13.365 transmembrane molecule because it's not NOTE Confidence: 0.9901895 00:28:13.365 --> 00:28:14.645 just an imaging molecule, but NOTE Confidence: 0.9901895 00:28:14.645 --> 00:28:15.765 it is a therapeutic one NOTE Confidence: 0.9901895 00:28:15.765 --> 00:28:16.645 as I'll talk about in NOTE Confidence: 0.9901895 00:28:16.645 --> 00:28:17.225 a second. NOTE Confidence: 0.9775276 00:28:18.005 --> 00:28:20.164 It's, highly expressed in prostate NOTE Confidence: 0.9775276 00:28:20.164 --> 00:28:20.664 cancer, NOTE Confidence: 0.9619466 00:28:21.044 --> 00:28:21.865 but particularly, NOTE Confidence: 0.9905092 00:28:22.325 --> 00:28:23.525 almost a thousand fold in NOTE Confidence: 0.9905092 00:28:23.525 --> 00:28:24.585 metastatic disease. NOTE Confidence: 0.9681257 00:28:24.900 --> 00:28:25.940 And one of the issues NOTE Confidence: 0.9681257 00:28:25.940 --> 00:28:27.460 is that this this, new NOTE Confidence: 0.9681257 00:28:27.460 --> 00:28:28.740 imaging agent became, you know, NOTE Confidence: 0.9681257 00:28:28.740 --> 00:28:30.520 became available relatively recently. NOTE Confidence: 0.98349375 00:28:30.900 --> 00:28:31.780 And you can see here, NOTE Confidence: 0.98349375 00:28:31.780 --> 00:28:33.060 I I listed the timing NOTE Confidence: 0.98349375 00:28:33.060 --> 00:28:34.420 when it became available, twenty NOTE Confidence: 0.98349375 00:28:34.420 --> 00:28:35.700 twenty, twenty twenty one, twenty NOTE Confidence: 0.98349375 00:28:35.700 --> 00:28:37.060 twenty three. These are three NOTE Confidence: 0.98349375 00:28:37.060 --> 00:28:39.080 different types of PSMA reagents. NOTE Confidence: 0.9873532 00:28:39.525 --> 00:28:40.485 And so in a very NOTE Confidence: 0.9873532 00:28:40.485 --> 00:28:41.925 short time, we've put a NOTE Confidence: 0.9873532 00:28:41.925 --> 00:28:42.965 lot of pressure on nuclear NOTE Confidence: 0.9873532 00:28:42.965 --> 00:28:44.165 medicine to be able to NOTE Confidence: 0.9873532 00:28:44.165 --> 00:28:45.205 get these scans for our NOTE Confidence: 0.9873532 00:28:45.205 --> 00:28:46.025 patients because NOTE Confidence: 0.9888157 00:28:46.325 --> 00:28:47.785 from the point of diagnosis NOTE Confidence: 0.9888157 00:28:47.925 --> 00:28:48.565 all the way to the NOTE Confidence: 0.9888157 00:28:48.565 --> 00:28:50.325 point of advanced disease, this NOTE Confidence: 0.9888157 00:28:50.325 --> 00:28:51.925 is helping guide exactly where NOTE Confidence: 0.9888157 00:28:51.925 --> 00:28:52.885 the cancer is in a NOTE Confidence: 0.9888157 00:28:52.885 --> 00:28:54.485 much more sensitive and specific NOTE Confidence: 0.9888157 00:28:54.485 --> 00:28:55.710 way than we were able NOTE Confidence: 0.9888157 00:28:55.710 --> 00:28:57.630 to do with, with, imaging NOTE Confidence: 0.9888157 00:28:57.630 --> 00:28:59.150 like bone scans or or NOTE Confidence: 0.9888157 00:28:59.150 --> 00:29:00.370 CT scans alone. NOTE Confidence: 0.99631375 00:29:00.990 --> 00:29:02.130 And, it is, NOTE Confidence: 0.98797095 00:29:02.670 --> 00:29:04.190 not real it's it's expressed NOTE Confidence: 0.98797095 00:29:04.190 --> 00:29:05.710 on other organs, particularly the NOTE Confidence: 0.98797095 00:29:05.710 --> 00:29:07.390 salivary and lacrimal glands. You'll NOTE Confidence: 0.98797095 00:29:07.390 --> 00:29:08.110 see on some of the NOTE Confidence: 0.98797095 00:29:08.110 --> 00:29:09.565 images I show you, which NOTE Confidence: 0.98797095 00:29:09.565 --> 00:29:10.765 is important because of the NOTE Confidence: 0.98797095 00:29:10.765 --> 00:29:12.205 toxicity of drugs that target NOTE Confidence: 0.98797095 00:29:12.205 --> 00:29:13.405 it. So they get dry NOTE Confidence: 0.98797095 00:29:13.405 --> 00:29:14.305 mouth, for example, NOTE Confidence: 0.99192274 00:29:15.085 --> 00:29:16.365 and the kidneys can also NOTE Confidence: 0.99192274 00:29:16.365 --> 00:29:18.045 sometimes take up these, some NOTE Confidence: 0.99192274 00:29:18.045 --> 00:29:19.245 of these drugs. But it NOTE Confidence: 0.99192274 00:29:19.245 --> 00:29:20.525 is a really important and NOTE Confidence: 0.99192274 00:29:20.525 --> 00:29:21.505 excellent target. NOTE Confidence: 0.7525256 00:29:22.685 --> 00:29:23.185 So, NOTE Confidence: 0.9946351 00:29:25.170 --> 00:29:26.450 so we we do know NOTE Confidence: 0.9946351 00:29:26.450 --> 00:29:27.990 that that concept of nonmetastatic NOTE Confidence: 0.9989401 00:29:28.370 --> 00:29:30.230 is a disappearing disease state. NOTE Confidence: 0.9948809 00:29:30.690 --> 00:29:31.650 So there were drugs that NOTE Confidence: 0.9948809 00:29:31.650 --> 00:29:32.950 were approved for nonmetastatic NOTE Confidence: 0.97050184 00:29:33.810 --> 00:29:35.890 castration resistant prostate cancer. But NOTE Confidence: 0.97050184 00:29:35.890 --> 00:29:36.930 in this study from the NOTE Confidence: 0.97050184 00:29:36.930 --> 00:29:37.430 UCLA, NOTE Confidence: 0.94174695 00:29:38.035 --> 00:29:39.395 when they looked at patients NOTE Confidence: 0.94174695 00:29:39.395 --> 00:29:40.295 who are nonmetastatic, NOTE Confidence: 0.95198685 00:29:40.915 --> 00:29:41.795 that is they didn't have NOTE Confidence: 0.95198685 00:29:41.795 --> 00:29:42.755 cancer on a bone or NOTE Confidence: 0.95198685 00:29:42.755 --> 00:29:44.035 CT scan and they did NOTE Confidence: 0.95198685 00:29:44.035 --> 00:29:45.175 a PSMA PET, NOTE Confidence: 0.98815817 00:29:45.635 --> 00:29:46.675 ninety six percent of them NOTE Confidence: 0.98815817 00:29:46.675 --> 00:29:48.035 were ninety ninety eight percent NOTE Confidence: 0.98815817 00:29:48.035 --> 00:29:48.915 of them actually had a NOTE Confidence: 0.98815817 00:29:48.915 --> 00:29:50.435 positive PET scan. So how NOTE Confidence: 0.98815817 00:29:50.515 --> 00:29:52.035 that's not nonmetastatic. It means NOTE Confidence: 0.98815817 00:29:52.035 --> 00:29:53.075 that your old scan was NOTE Confidence: 0.98815817 00:29:53.075 --> 00:29:53.735 no good. NOTE Confidence: 0.99424726 00:29:54.090 --> 00:29:55.530 And so it is a NOTE Confidence: 0.99424726 00:29:55.530 --> 00:29:57.049 disappearing disease state in in NOTE Confidence: 0.99424726 00:29:57.049 --> 00:29:58.350 the advent of the PSMA NOTE Confidence: 0.99424726 00:29:58.410 --> 00:29:58.910 era. NOTE Confidence: 0.9996011 00:30:00.010 --> 00:30:01.070 There was a prior NOTE Confidence: 0.9778338 00:30:01.610 --> 00:30:03.049 test that was available a NOTE Confidence: 0.9778338 00:30:03.049 --> 00:30:04.510 few years before called fluciclovine. NOTE Confidence: 0.9778338 00:30:04.730 --> 00:30:06.730 Fluciclovine is interesting because it NOTE Confidence: 0.9778338 00:30:06.730 --> 00:30:08.265 is a metabolic scan. It's NOTE Confidence: 0.9778338 00:30:08.345 --> 00:30:10.205 an amino acid, that, NOTE Confidence: 0.990639 00:30:10.825 --> 00:30:11.785 that was used that we NOTE Confidence: 0.990639 00:30:11.785 --> 00:30:13.145 were using before PSMA became NOTE Confidence: 0.990639 00:30:13.145 --> 00:30:14.345 widely available in the United NOTE Confidence: 0.990639 00:30:14.345 --> 00:30:15.465 States. And this was a NOTE Confidence: 0.990639 00:30:15.465 --> 00:30:16.765 head to head study comparing NOTE Confidence: 0.9582556 00:30:17.225 --> 00:30:18.925 PSMA to fluciclovine. NOTE Confidence: 0.9992606 00:30:19.305 --> 00:30:20.520 And you can see that NOTE Confidence: 0.9992606 00:30:20.680 --> 00:30:22.520 PSMA was four point eight NOTE Confidence: 0.9992606 00:30:22.520 --> 00:30:24.280 times more accurate in terms NOTE Confidence: 0.9992606 00:30:24.280 --> 00:30:25.100 of detecting, NOTE Confidence: 0.97971153 00:30:26.200 --> 00:30:28.540 detecting prostate cancer. So, again, NOTE Confidence: 0.9789014 00:30:29.160 --> 00:30:30.600 you can't treat what you NOTE Confidence: 0.9789014 00:30:30.600 --> 00:30:32.280 can't measure. Right? We have NOTE Confidence: 0.9789014 00:30:32.280 --> 00:30:33.640 PSA. We can measure that. NOTE Confidence: 0.9789014 00:30:33.640 --> 00:30:34.905 That's a very simple quick NOTE Confidence: 0.9789014 00:30:34.905 --> 00:30:35.785 test that we can order NOTE Confidence: 0.9789014 00:30:35.785 --> 00:30:37.305 on these patients. It's not NOTE Confidence: 0.9789014 00:30:37.305 --> 00:30:38.425 perfect. It doesn't give us NOTE Confidence: 0.9789014 00:30:38.425 --> 00:30:39.625 all the information. Certainly doesn't NOTE Confidence: 0.9789014 00:30:39.625 --> 00:30:41.385 tell us where the cancer NOTE Confidence: 0.9789014 00:30:41.385 --> 00:30:42.845 is, and that's why PSMA NOTE Confidence: 0.9613394 00:30:43.545 --> 00:30:44.985 PET in particular has really NOTE Confidence: 0.9613394 00:30:44.985 --> 00:30:46.105 transformed the way we think NOTE Confidence: 0.9613394 00:30:46.105 --> 00:30:47.005 about this disease. NOTE Confidence: 0.9741432 00:30:48.380 --> 00:30:50.139 And, this is a prelude NOTE Confidence: 0.9741432 00:30:50.139 --> 00:30:51.500 to the the next section NOTE Confidence: 0.9741432 00:30:51.500 --> 00:30:52.539 of my talk, which is NOTE Confidence: 0.9741432 00:30:52.539 --> 00:30:53.279 really therapeutics. NOTE Confidence: 0.9953484 00:30:53.740 --> 00:30:54.620 Because as you see on NOTE Confidence: 0.9953484 00:30:54.620 --> 00:30:55.419 the left, you can see NOTE Confidence: 0.9953484 00:30:55.419 --> 00:30:57.120 a patient with metastatic disease NOTE Confidence: 0.9953484 00:30:57.259 --> 00:30:58.940 who has a positive PSMA NOTE Confidence: 0.9953484 00:30:58.940 --> 00:30:59.980 PET scan. You can see NOTE Confidence: 0.9953484 00:30:59.980 --> 00:31:01.179 the the areas in his NOTE Confidence: 0.9953484 00:31:01.179 --> 00:31:01.679 bone, NOTE Confidence: 0.9963035 00:31:01.980 --> 00:31:03.015 that light up. NOTE Confidence: 0.98315716 00:31:03.415 --> 00:31:04.475 You can see the salivary NOTE Confidence: 0.98315716 00:31:04.535 --> 00:31:05.655 glands up in the upper NOTE Confidence: 0.98315716 00:31:05.655 --> 00:31:07.015 part of his head, and, NOTE Confidence: 0.98148185 00:31:07.655 --> 00:31:08.535 and you can also see NOTE Confidence: 0.98148185 00:31:08.535 --> 00:31:09.655 that his kidneys light up NOTE Confidence: 0.98148185 00:31:09.655 --> 00:31:10.935 because it's being excreted through NOTE Confidence: 0.98148185 00:31:10.935 --> 00:31:12.375 the kidneys, and some is, NOTE Confidence: 0.98148185 00:31:12.535 --> 00:31:13.755 collecting in the bladder. NOTE Confidence: 0.98232204 00:31:14.135 --> 00:31:15.175 On the right side, you NOTE Confidence: 0.98232204 00:31:15.175 --> 00:31:15.835 see that, NOTE Confidence: 0.9838325 00:31:16.370 --> 00:31:17.570 FDG PET, which has been NOTE Confidence: 0.9838325 00:31:17.570 --> 00:31:18.610 around for many years and NOTE Confidence: 0.9838325 00:31:18.610 --> 00:31:19.570 and really lights up in NOTE Confidence: 0.9838325 00:31:19.570 --> 00:31:20.690 the with the advent of NOTE Confidence: 0.9838325 00:31:20.690 --> 00:31:21.190 glucose NOTE Confidence: 0.96527976 00:31:21.570 --> 00:31:23.090 and is very useful in NOTE Confidence: 0.96527976 00:31:23.090 --> 00:31:24.610 diseases like lymphoma and lung NOTE Confidence: 0.96527976 00:31:24.610 --> 00:31:26.690 cancer because those cancers are NOTE Confidence: 0.96527976 00:31:26.690 --> 00:31:28.130 very proliferative and use quite NOTE Confidence: 0.96527976 00:31:28.130 --> 00:31:29.030 a lot of glucose. NOTE Confidence: 0.9452557 00:31:29.410 --> 00:31:30.630 That that sometimes, NOTE Confidence: 0.97225523 00:31:31.414 --> 00:31:33.015 in traditionally, FDG PET was NOTE Confidence: 0.97225523 00:31:33.015 --> 00:31:34.375 not useful in prostate cancer. NOTE Confidence: 0.97225523 00:31:34.375 --> 00:31:35.654 Traditionally, we haven't used a NOTE Confidence: 0.97225523 00:31:35.654 --> 00:31:36.455 lot of it, but you NOTE Confidence: 0.97225523 00:31:36.455 --> 00:31:37.654 can see that, in fact, NOTE Confidence: 0.97225523 00:31:37.654 --> 00:31:39.095 there are some cancers in NOTE Confidence: 0.97225523 00:31:39.174 --> 00:31:40.715 including in this patient here NOTE Confidence: 0.97225523 00:31:40.855 --> 00:31:42.215 where some of the cancer NOTE Confidence: 0.97225523 00:31:42.215 --> 00:31:44.054 cells do express PSMA, but NOTE Confidence: 0.97225523 00:31:44.054 --> 00:31:45.640 some don't, and they only NOTE Confidence: 0.97225523 00:31:45.640 --> 00:31:47.240 express FDG. And that's as NOTE Confidence: 0.97225523 00:31:47.240 --> 00:31:48.200 you'll see in a minute, NOTE Confidence: 0.97225523 00:31:48.200 --> 00:31:49.240 that's a real issue as NOTE Confidence: 0.97225523 00:31:49.240 --> 00:31:50.380 we learn more about, NOTE Confidence: 0.9678294 00:31:50.920 --> 00:31:52.200 the use of these imaging NOTE Confidence: 0.9678294 00:31:52.200 --> 00:31:53.020 tech techniques. NOTE Confidence: 0.9732318 00:31:53.880 --> 00:31:54.920 So the last section of NOTE Confidence: 0.9732318 00:31:54.920 --> 00:31:56.040 my talk is really gonna, NOTE Confidence: 0.9732318 00:31:56.360 --> 00:31:57.480 focus on this era of NOTE Confidence: 0.9732318 00:31:57.480 --> 00:31:59.385 targeted therapy. I already started NOTE Confidence: 0.9732318 00:31:59.385 --> 00:32:00.985 by saying androgen receptor pathway NOTE Confidence: 0.9732318 00:32:00.985 --> 00:32:02.345 inhibitors are targeted therapy, and NOTE Confidence: 0.9732318 00:32:02.345 --> 00:32:04.185 that's true. But in fact, NOTE Confidence: 0.9732318 00:32:04.185 --> 00:32:05.865 we're moving to, an era NOTE Confidence: 0.9732318 00:32:05.865 --> 00:32:06.525 of radioligands, NOTE Confidence: 0.9897077 00:32:07.465 --> 00:32:09.325 bispecifics, and beyond. So, NOTE Confidence: 0.98042876 00:32:10.025 --> 00:32:11.485 so this is, really NOTE Confidence: 0.97749364 00:32:11.929 --> 00:32:13.210 in in this case, I'm NOTE Confidence: 0.97749364 00:32:13.210 --> 00:32:14.330 gonna talk about LU one NOTE Confidence: 0.97749364 00:32:14.330 --> 00:32:15.390 seven seven PSMA, NOTE Confidence: 0.96229094 00:32:15.850 --> 00:32:17.210 but we're also gonna talk NOTE Confidence: 0.96229094 00:32:17.210 --> 00:32:18.570 about all the treatments that NOTE Confidence: 0.96229094 00:32:18.570 --> 00:32:19.530 I think are are on NOTE Confidence: 0.96229094 00:32:19.530 --> 00:32:21.130 their way. So this was NOTE Confidence: 0.96229094 00:32:21.130 --> 00:32:22.570 a, New England Journal paper NOTE Confidence: 0.96229094 00:32:22.570 --> 00:32:23.929 just three years ago now NOTE Confidence: 0.96229094 00:32:23.929 --> 00:32:25.150 called the VISION study. NOTE Confidence: 0.9549279 00:32:25.615 --> 00:32:26.654 And it really shows you NOTE Confidence: 0.9549279 00:32:26.654 --> 00:32:28.255 how PSMA, in particular a NOTE Confidence: 0.9549279 00:32:28.255 --> 00:32:29.775 ligand called PSMA six one NOTE Confidence: 0.9549279 00:32:29.775 --> 00:32:31.455 seven, binds to the cancer NOTE Confidence: 0.9549279 00:32:31.455 --> 00:32:32.755 cell and delivers NOTE Confidence: 0.99456245 00:32:33.294 --> 00:32:34.115 a radioactive, NOTE Confidence: 0.9622645 00:32:34.735 --> 00:32:36.255 payload. In this case, LU NOTE Confidence: 0.9622645 00:32:36.255 --> 00:32:37.740 one seven seven. That's a NOTE Confidence: 0.9622645 00:32:37.900 --> 00:32:39.420 a beta particle that is NOTE Confidence: 0.9622645 00:32:39.420 --> 00:32:41.020 lethal. So remember the imaging NOTE Confidence: 0.9622645 00:32:41.020 --> 00:32:42.140 I showed you earlier was NOTE Confidence: 0.9622645 00:32:42.140 --> 00:32:43.020 just to see the pic NOTE Confidence: 0.9622645 00:32:43.340 --> 00:32:44.460 where the cancer is. But NOTE Confidence: 0.9622645 00:32:44.460 --> 00:32:45.900 if you put a attach NOTE Confidence: 0.9622645 00:32:45.900 --> 00:32:46.800 it to a radio, NOTE Confidence: 0.98274094 00:32:47.260 --> 00:32:48.480 ligand that actually, NOTE Confidence: 0.9767832 00:32:48.940 --> 00:32:50.460 is in endocytosed by the NOTE Confidence: 0.9767832 00:32:50.460 --> 00:32:51.820 tumor cell, then it destroys NOTE Confidence: 0.9767832 00:32:51.820 --> 00:32:52.965 that that cancer cell. That's NOTE Confidence: 0.9767832 00:32:52.965 --> 00:32:53.924 the idea. So it's like NOTE Confidence: 0.9767832 00:32:53.924 --> 00:32:55.065 a smart bomb technology NOTE Confidence: 0.9942823 00:32:55.684 --> 00:32:57.765 to take PSMA and then NOTE Confidence: 0.9942823 00:32:57.765 --> 00:32:58.265 deliver, NOTE Confidence: 0.97936326 00:32:59.125 --> 00:33:00.424 a radioactive particle. NOTE Confidence: 0.97542506 00:33:01.285 --> 00:33:02.405 And this is a trial NOTE Confidence: 0.97542506 00:33:02.405 --> 00:33:03.605 design. You had to just NOTE Confidence: 0.97542506 00:33:03.605 --> 00:33:05.625 have one positive PSMA, NOTE Confidence: 0.97971755 00:33:06.000 --> 00:33:07.200 PET lesion. And we can NOTE Confidence: 0.97971755 00:33:07.200 --> 00:33:08.000 talk a little bit about NOTE Confidence: 0.97971755 00:33:08.000 --> 00:33:10.020 the nuances of this, but NOTE Confidence: 0.97971755 00:33:10.080 --> 00:33:11.120 this makes it very simple. NOTE Confidence: 0.97971755 00:33:11.120 --> 00:33:12.000 When you're doing a large NOTE Confidence: 0.97971755 00:33:12.000 --> 00:33:13.920 randomized trials, keep it simple. NOTE Confidence: 0.97971755 00:33:13.920 --> 00:33:14.800 If you don't keep it NOTE Confidence: 0.97971755 00:33:14.800 --> 00:33:15.760 simple, it's very hard to NOTE Confidence: 0.97971755 00:33:15.760 --> 00:33:16.580 accrue patients. NOTE Confidence: 0.99160683 00:33:17.120 --> 00:33:18.480 And the the advantage of NOTE Confidence: 0.99160683 00:33:18.480 --> 00:33:19.815 this treatment is that the NOTE Confidence: 0.99160683 00:33:19.815 --> 00:33:20.695 patients could have had it NOTE Confidence: 0.99160683 00:33:20.695 --> 00:33:22.054 anywhere. It works wherever the NOTE Confidence: 0.99160683 00:33:22.054 --> 00:33:23.174 cancer is. It works if NOTE Confidence: 0.99160683 00:33:23.174 --> 00:33:23.975 it's in the bone, in NOTE Confidence: 0.99160683 00:33:23.975 --> 00:33:24.855 the lymph nodes, in the NOTE Confidence: 0.99160683 00:33:24.855 --> 00:33:25.674 liver, anywhere. NOTE Confidence: 0.99422485 00:33:26.774 --> 00:33:28.154 And the patients were randomized. NOTE Confidence: 0.97135246 00:33:28.615 --> 00:33:29.575 These are patients who had NOTE Confidence: 0.97135246 00:33:29.575 --> 00:33:30.934 already received the standard of NOTE Confidence: 0.97135246 00:33:30.934 --> 00:33:31.815 care at the time, which NOTE Confidence: 0.97135246 00:33:31.815 --> 00:33:33.755 included chemotherapy with a taxane NOTE Confidence: 0.9002595 00:33:34.500 --> 00:33:35.880 or, an ARPY, NOTE Confidence: 0.9858569 00:33:36.340 --> 00:33:37.000 or both. NOTE Confidence: 0.95971745 00:33:37.300 --> 00:33:38.660 And they were randomized to NOTE Confidence: 0.95971745 00:33:38.660 --> 00:33:40.180 receive standard of care therapy, NOTE Confidence: 0.95971745 00:33:40.180 --> 00:33:41.720 which was not further chemotherapy NOTE Confidence: 0.95971745 00:33:41.780 --> 00:33:44.020 but anything else, versus this, NOTE Confidence: 0.9792815 00:33:44.580 --> 00:33:45.780 treatment, l u one seven NOTE Confidence: 0.9792815 00:33:45.780 --> 00:33:46.840 seven six PSMA. NOTE Confidence: 0.99059695 00:33:47.380 --> 00:33:48.520 And you can see here, NOTE Confidence: 0.97828686 00:33:48.904 --> 00:33:50.825 on the left, radiographic progression NOTE Confidence: 0.97828686 00:33:50.825 --> 00:33:51.565 free survival, NOTE Confidence: 0.96825504 00:33:52.265 --> 00:33:53.705 hazard ratio of point four NOTE Confidence: 0.96825504 00:33:53.705 --> 00:33:54.205 zero, NOTE Confidence: 0.9322068 00:33:54.505 --> 00:33:56.105 sixty percent reduction in risk NOTE Confidence: 0.9322068 00:33:56.105 --> 00:33:57.784 of project progression. But more NOTE Confidence: 0.9322068 00:33:57.784 --> 00:33:59.784 importantly, overall survival, point six NOTE Confidence: 0.9322068 00:33:59.784 --> 00:34:01.279 two has a ratio, Forty NOTE Confidence: 0.9322068 00:34:01.279 --> 00:34:02.980 percent improvement in overall survival. NOTE Confidence: 0.97346383 00:34:03.360 --> 00:34:04.240 And we have seen some NOTE Confidence: 0.97346383 00:34:04.240 --> 00:34:06.000 dramatic responses to patients with NOTE Confidence: 0.97346383 00:34:06.000 --> 00:34:07.679 this treatment. It is, given NOTE Confidence: 0.97346383 00:34:07.679 --> 00:34:09.280 here, and it is, it NOTE Confidence: 0.97346383 00:34:09.280 --> 00:34:10.480 has transformed a lot of NOTE Confidence: 0.97346383 00:34:10.480 --> 00:34:11.140 my patients', NOTE Confidence: 0.9981853 00:34:11.839 --> 00:34:12.339 lives. NOTE Confidence: 0.9763749 00:34:13.040 --> 00:34:14.275 It is not curative, at NOTE Confidence: 0.9763749 00:34:14.275 --> 00:34:15.395 least in the states we're NOTE Confidence: 0.9763749 00:34:15.395 --> 00:34:16.515 giving. Remember, we're giving it NOTE Confidence: 0.9763749 00:34:16.515 --> 00:34:17.795 at very late stages right NOTE Confidence: 0.9763749 00:34:17.795 --> 00:34:18.295 now. NOTE Confidence: 0.9985785 00:34:18.675 --> 00:34:19.635 So we'll talk a little NOTE Confidence: 0.9985785 00:34:19.635 --> 00:34:21.235 bit about, what's being done NOTE Confidence: 0.9985785 00:34:21.235 --> 00:34:22.215 to move it forward. NOTE Confidence: 0.9886123 00:34:23.395 --> 00:34:24.435 So if you look at NOTE Confidence: 0.9886123 00:34:24.435 --> 00:34:26.035 PSA response, that's a very NOTE Confidence: 0.9886123 00:34:26.035 --> 00:34:27.494 common way that we measure NOTE Confidence: 0.9886123 00:34:27.710 --> 00:34:29.309 how efficacious a treatment is. NOTE Confidence: 0.9886123 00:34:29.309 --> 00:34:30.349 And you can see that NOTE Confidence: 0.9886123 00:34:30.349 --> 00:34:31.170 if you use, NOTE Confidence: 0.9780767 00:34:31.950 --> 00:34:33.309 standard of care alone, about NOTE Confidence: 0.9780767 00:34:33.309 --> 00:34:34.269 seven percent will have a NOTE Confidence: 0.9780767 00:34:34.269 --> 00:34:35.730 fifty percent drop in PSA. NOTE Confidence: 0.9780767 00:34:35.869 --> 00:34:36.829 But if you use this NOTE Confidence: 0.9780767 00:34:36.829 --> 00:34:38.289 LU one seven seven, NOTE Confidence: 0.9876847 00:34:38.670 --> 00:34:40.065 it's about forty six percent. NOTE Confidence: 0.9876847 00:34:40.224 --> 00:34:41.265 So, again, this is not NOTE Confidence: 0.9876847 00:34:41.265 --> 00:34:42.224 a treatment that works in NOTE Confidence: 0.9876847 00:34:42.224 --> 00:34:43.185 every patient. We can talk NOTE Confidence: 0.9876847 00:34:43.185 --> 00:34:44.244 about some of the nuances NOTE Confidence: 0.9876847 00:34:44.305 --> 00:34:45.425 there, but this is a NOTE Confidence: 0.9876847 00:34:45.425 --> 00:34:46.464 group of patients who had NOTE Confidence: 0.9876847 00:34:46.464 --> 00:34:47.665 no other therapy available to NOTE Confidence: 0.9876847 00:34:47.665 --> 00:34:49.025 them and who were likely NOTE Confidence: 0.9876847 00:34:49.025 --> 00:34:50.244 to progress and die. NOTE Confidence: 0.9717007 00:34:51.344 --> 00:34:53.125 And we definitely see exceptional NOTE Confidence: 0.9717007 00:34:53.185 --> 00:34:54.305 responders. And what you see NOTE Confidence: 0.9717007 00:34:54.305 --> 00:34:55.410 here in this patient is NOTE Confidence: 0.9717007 00:34:55.489 --> 00:34:56.450 on the left side, his NOTE Confidence: 0.9717007 00:34:56.450 --> 00:34:57.089 PSA was, NOTE Confidence: 0.9536574 00:34:57.650 --> 00:34:59.089 eight hundred and eighty, and NOTE Confidence: 0.9536574 00:34:59.089 --> 00:35:00.950 he had diffuse bone metastases NOTE Confidence: 0.9536574 00:35:01.010 --> 00:35:02.069 as you can see there. NOTE Confidence: 0.9536574 00:35:02.289 --> 00:35:03.809 And within, one month and NOTE Confidence: 0.9536574 00:35:03.809 --> 00:35:04.770 then three months, which you NOTE Confidence: 0.9536574 00:35:04.770 --> 00:35:05.569 see on the second to NOTE Confidence: 0.9536574 00:35:05.569 --> 00:35:07.329 last and last panel, his NOTE Confidence: 0.9536574 00:35:07.329 --> 00:35:08.289 PSA has gone down to NOTE Confidence: 0.9536574 00:35:08.289 --> 00:35:10.130 thirty and his bones, his, NOTE Confidence: 0.9536574 00:35:10.450 --> 00:35:12.194 PET scan is pretty much, NOTE Confidence: 0.772979 00:35:13.055 --> 00:35:13.555 clear, NOTE Confidence: 0.988293 00:35:13.934 --> 00:35:15.375 almost completely clear. And we've NOTE Confidence: 0.988293 00:35:15.375 --> 00:35:16.815 seen some complete responses with NOTE Confidence: 0.988293 00:35:16.815 --> 00:35:17.555 these treatments. NOTE Confidence: 0.999734 00:35:17.855 --> 00:35:18.355 So NOTE Confidence: 0.99924564 00:35:18.734 --> 00:35:20.094 it is a smart way NOTE Confidence: 0.99924564 00:35:20.094 --> 00:35:21.954 of delivering targeted radiopharmaceutical NOTE Confidence: 0.9720528 00:35:22.415 --> 00:35:22.915 therapy. NOTE Confidence: 0.9692561 00:35:23.295 --> 00:35:24.390 But as I mentioned in NOTE Confidence: 0.9692561 00:35:24.390 --> 00:35:25.829 that earlier graphic where I NOTE Confidence: 0.9692561 00:35:25.829 --> 00:35:26.950 showed it next to FTG NOTE Confidence: 0.9692561 00:35:26.950 --> 00:35:28.790 PET, there are still patients, NOTE Confidence: 0.9692561 00:35:28.790 --> 00:35:30.390 for example, who don't express NOTE Confidence: 0.9692561 00:35:30.390 --> 00:35:31.750 PSMA. That's what you see NOTE Confidence: 0.9692561 00:35:31.750 --> 00:35:33.270 in the left panel. Or NOTE Confidence: 0.9692561 00:35:33.270 --> 00:35:34.950 patients who have discordance between NOTE Confidence: 0.9692561 00:35:34.950 --> 00:35:36.089 PSMA and FDG, NOTE Confidence: 0.9622322 00:35:36.545 --> 00:35:37.505 either in bone in the NOTE Confidence: 0.9622322 00:35:37.505 --> 00:35:38.625 center panels or in the NOTE Confidence: 0.9622322 00:35:38.625 --> 00:35:39.665 right. And you see I NOTE Confidence: 0.9622322 00:35:39.665 --> 00:35:41.025 put PSMA at next to NOTE Confidence: 0.9622322 00:35:41.025 --> 00:35:42.485 FDG in each of these, NOTE Confidence: 0.9622322 00:35:42.545 --> 00:35:43.505 and you can see that NOTE Confidence: 0.9622322 00:35:43.505 --> 00:35:45.025 in some patients, the FDG NOTE Confidence: 0.9622322 00:35:45.025 --> 00:35:46.465 PET is showing tumors that NOTE Confidence: 0.9622322 00:35:46.465 --> 00:35:47.445 don't make PSMA. NOTE Confidence: 0.92797405 00:35:48.625 --> 00:35:49.905 This is also as probably NOTE Confidence: 0.92797405 00:35:49.905 --> 00:35:50.945 a a a a way NOTE Confidence: 0.92797405 00:35:50.945 --> 00:35:52.325 in which these cancer cells, NOTE Confidence: 0.95125246 00:35:52.839 --> 00:35:53.640 you know, it's like the NOTE Confidence: 0.95125246 00:35:53.640 --> 00:35:55.079 terminator. Sometimes you you you NOTE Confidence: 0.95125246 00:35:55.079 --> 00:35:56.440 shrink them as many as NOTE Confidence: 0.95125246 00:35:56.440 --> 00:35:57.319 you can, but the cancer NOTE Confidence: 0.95125246 00:35:57.319 --> 00:35:58.380 cells that recur NOTE Confidence: 0.9530772 00:35:58.680 --> 00:36:00.280 are don't express PSMA. And NOTE Confidence: 0.9530772 00:36:00.280 --> 00:36:01.400 and this treatment will not NOTE Confidence: 0.9530772 00:36:01.400 --> 00:36:02.440 work if your tumor cell NOTE Confidence: 0.9530772 00:36:02.440 --> 00:36:03.579 does not make PSMA. NOTE Confidence: 0.99219936 00:36:04.725 --> 00:36:05.925 The side effects are almost NOTE Confidence: 0.99219936 00:36:05.925 --> 00:36:06.905 what you'd expect. NOTE Confidence: 0.9973525 00:36:07.685 --> 00:36:08.745 Because it's a radiopharmaceutical, NOTE Confidence: 0.97528225 00:36:09.605 --> 00:36:10.885 we see bone marrow suppression NOTE Confidence: 0.97528225 00:36:10.885 --> 00:36:11.625 and fatigue. NOTE Confidence: 0.96929777 00:36:12.405 --> 00:36:13.445 And the dry mouth is NOTE Confidence: 0.96929777 00:36:13.445 --> 00:36:15.225 unique to this treatment because NOTE Confidence: 0.96929777 00:36:15.285 --> 00:36:16.085 as I showed you in NOTE Confidence: 0.96929777 00:36:16.085 --> 00:36:17.205 some of those graphics, you NOTE Confidence: 0.96929777 00:36:17.205 --> 00:36:17.864 see this, NOTE Confidence: 0.9192163 00:36:18.680 --> 00:36:19.980 this uptake in the salivary NOTE Confidence: 0.9192163 00:36:20.120 --> 00:36:21.180 and, glands. NOTE Confidence: 0.9828026 00:36:21.800 --> 00:36:22.840 So what about moving this NOTE Confidence: 0.9828026 00:36:22.840 --> 00:36:24.040 treatment earlier? Like, why are NOTE Confidence: 0.9828026 00:36:24.040 --> 00:36:25.160 we waiting until after the NOTE Confidence: 0.9828026 00:36:25.160 --> 00:36:27.000 patient's progressed on chemotherapy and NOTE Confidence: 0.9828026 00:36:27.000 --> 00:36:28.280 has the amount of disease NOTE Confidence: 0.9828026 00:36:28.280 --> 00:36:29.720 I showed you? Well, that NOTE Confidence: 0.9828026 00:36:29.720 --> 00:36:31.480 idea is obviously, moving forward. NOTE Confidence: 0.9828026 00:36:31.480 --> 00:36:32.360 And this was a study NOTE Confidence: 0.9828026 00:36:32.360 --> 00:36:34.205 called PSMA four. This is NOTE Confidence: 0.9828026 00:36:34.205 --> 00:36:35.344 before chemotherapy. NOTE Confidence: 0.9963772 00:36:35.885 --> 00:36:36.765 And you can see it's NOTE Confidence: 0.9963772 00:36:36.765 --> 00:36:37.585 the same randomization. NOTE Confidence: 0.9503776 00:36:37.885 --> 00:36:39.265 You could either get another NOTE Confidence: 0.9503776 00:36:39.565 --> 00:36:40.605 ARPI or you could get, NOTE Confidence: 0.9503776 00:36:40.844 --> 00:36:42.445 this LU one seven seven. NOTE Confidence: 0.9503776 00:36:42.445 --> 00:36:43.165 And you see on the NOTE Confidence: 0.9503776 00:36:43.165 --> 00:36:44.765 left side a very strong NOTE Confidence: 0.9503776 00:36:44.765 --> 00:36:45.265 PSMA, NOTE Confidence: 0.93413395 00:36:47.390 --> 00:36:49.630 PFS benefit. So really a NOTE Confidence: 0.93413395 00:36:49.630 --> 00:36:50.750 doubling of the time it NOTE Confidence: 0.93413395 00:36:50.750 --> 00:36:51.730 takes to progress. NOTE Confidence: 0.9736641 00:36:52.030 --> 00:36:52.830 But on the right side, NOTE Confidence: 0.9736641 00:36:52.830 --> 00:36:53.950 you don't really see an NOTE Confidence: 0.9736641 00:36:53.950 --> 00:36:55.630 overall survival benefit. So this NOTE Confidence: 0.9736641 00:36:55.630 --> 00:36:56.510 is one of the reasons NOTE Confidence: 0.9736641 00:36:56.510 --> 00:36:57.550 that the FDA has not NOTE Confidence: 0.9736641 00:36:57.550 --> 00:36:58.590 yet approved this. This study NOTE Confidence: 0.9736641 00:36:58.590 --> 00:36:59.550 was presented, you can see NOTE Confidence: 0.9736641 00:36:59.550 --> 00:37:00.930 here, in twenty twenty three. NOTE Confidence: 0.9941798 00:37:01.235 --> 00:37:02.275 And we've seen this data NOTE Confidence: 0.9941798 00:37:02.275 --> 00:37:03.395 for quite some time, but NOTE Confidence: 0.9941798 00:37:03.395 --> 00:37:04.995 it's expected that the FDA NOTE Confidence: 0.9941798 00:37:04.995 --> 00:37:05.735 will actually, NOTE Confidence: 0.99714863 00:37:06.675 --> 00:37:08.195 probably approve this in patients NOTE Confidence: 0.99714863 00:37:08.195 --> 00:37:09.315 who have not yet received NOTE Confidence: 0.99714863 00:37:09.315 --> 00:37:10.995 chemotherapy. But it's, again, a NOTE Confidence: 0.99714863 00:37:10.995 --> 00:37:12.614 subject we don't fully understand NOTE Confidence: 0.90754014 00:37:12.995 --> 00:37:14.355 why are aren't these patients, NOTE Confidence: 0.90754014 00:37:14.594 --> 00:37:15.875 benefiting in terms of overall NOTE Confidence: 0.90754014 00:37:15.875 --> 00:37:16.375 survival. NOTE Confidence: 0.99139816 00:37:17.289 --> 00:37:18.329 And then the other question NOTE Confidence: 0.99139816 00:37:18.329 --> 00:37:19.450 is, you know, if if NOTE Confidence: 0.99139816 00:37:19.450 --> 00:37:20.410 this is these are all NOTE Confidence: 0.99139816 00:37:20.410 --> 00:37:21.869 patients with metastatic disease, NOTE Confidence: 0.92318726 00:37:22.650 --> 00:37:23.849 why wait till they develop NOTE Confidence: 0.92318726 00:37:23.849 --> 00:37:25.769 castration resistance? Why not just NOTE Confidence: 0.92318726 00:37:25.769 --> 00:37:26.670 treat them upfront? NOTE Confidence: 0.9432207 00:37:27.130 --> 00:37:28.170 And this was a study NOTE Confidence: 0.9432207 00:37:28.170 --> 00:37:29.690 from your, Australia where they NOTE Confidence: 0.9432207 00:37:29.690 --> 00:37:30.730 gave them two cycles of NOTE Confidence: 0.9432207 00:37:30.730 --> 00:37:32.394 PSMA treatment in addition to NOTE Confidence: 0.9432207 00:37:32.394 --> 00:37:33.994 hormones and chemotherapy. Remember I NOTE Confidence: 0.9432207 00:37:33.994 --> 00:37:35.454 told you, in MHSPC NOTE Confidence: 0.9567734 00:37:35.835 --> 00:37:37.594 combination therapy with two or NOTE Confidence: 0.9567734 00:37:37.594 --> 00:37:38.714 three drugs is the standard NOTE Confidence: 0.9567734 00:37:38.714 --> 00:37:40.075 of care. So why not NOTE Confidence: 0.9567734 00:37:40.075 --> 00:37:41.755 just give them this, two NOTE Confidence: 0.9567734 00:37:41.755 --> 00:37:43.614 treatments of PSMA in addition? NOTE Confidence: 0.9567734 00:37:43.914 --> 00:37:44.954 And they looked at, this NOTE Confidence: 0.9567734 00:37:44.954 --> 00:37:46.634 endpoint, which was after all NOTE Confidence: 0.9567734 00:37:46.634 --> 00:37:47.810 the treatment's done a a NOTE Confidence: 0.9567734 00:37:47.810 --> 00:37:49.410 year later, who's more likely NOTE Confidence: 0.9567734 00:37:49.410 --> 00:37:50.450 to have a low PSA? NOTE Confidence: 0.9567734 00:37:50.450 --> 00:37:51.650 And it was actually you NOTE Confidence: 0.9567734 00:37:51.650 --> 00:37:52.850 were four times more likely NOTE Confidence: 0.9567734 00:37:52.850 --> 00:37:53.989 to have a low PSA NOTE Confidence: 0.9567734 00:37:54.210 --> 00:37:55.030 a year later. NOTE Confidence: 0.9571547 00:37:55.410 --> 00:37:57.330 So it suggests actually that NOTE Confidence: 0.9571547 00:37:57.330 --> 00:37:59.010 giving this treatment upfront will NOTE Confidence: 0.9571547 00:37:59.010 --> 00:38:00.230 have a long term benefit. NOTE Confidence: 0.9975024 00:38:00.695 --> 00:38:01.195 Now, NOTE Confidence: 0.9992842 00:38:01.655 --> 00:38:03.094 there's another study giving six NOTE Confidence: 0.9992842 00:38:03.094 --> 00:38:04.295 of these cycles six of NOTE Confidence: 0.9992842 00:38:04.295 --> 00:38:04.955 these treatments. NOTE Confidence: 0.97985345 00:38:05.494 --> 00:38:06.455 If if you give a NOTE Confidence: 0.97985345 00:38:06.455 --> 00:38:08.295 treatment like hormonal therapy or NOTE Confidence: 0.97985345 00:38:08.295 --> 00:38:08.795 chemotherapy, NOTE Confidence: 0.99423397 00:38:09.175 --> 00:38:10.295 then the target starts to NOTE Confidence: 0.99423397 00:38:10.295 --> 00:38:12.295 go away. Will giving four NOTE Confidence: 0.99423397 00:38:12.295 --> 00:38:13.860 more of those cycles of NOTE Confidence: 0.99423397 00:38:14.100 --> 00:38:15.540 of of LU one seven NOTE Confidence: 0.99423397 00:38:15.540 --> 00:38:16.420 seven get rid of more NOTE Confidence: 0.99423397 00:38:16.420 --> 00:38:18.100 cancer? It's not clear. In NOTE Confidence: 0.99423397 00:38:18.100 --> 00:38:19.380 fact, when we give these NOTE Confidence: 0.99423397 00:38:19.380 --> 00:38:20.420 treatments to patients who have NOTE Confidence: 0.99423397 00:38:20.420 --> 00:38:21.380 a negative PET scan, it NOTE Confidence: 0.99423397 00:38:21.380 --> 00:38:22.980 doesn't work. It only works NOTE Confidence: 0.99423397 00:38:22.980 --> 00:38:24.360 if the target's there. NOTE Confidence: 0.98839426 00:38:24.660 --> 00:38:26.745 So I think, what these NOTE Confidence: 0.98839426 00:38:26.985 --> 00:38:28.505 studies suggest is earlier use NOTE Confidence: 0.98839426 00:38:28.505 --> 00:38:29.885 of these drugs does matter, NOTE Confidence: 0.98839426 00:38:30.025 --> 00:38:30.525 but NOTE Confidence: 0.9983365 00:38:30.985 --> 00:38:32.045 giving it indiscriminately NOTE Confidence: 0.99547255 00:38:32.345 --> 00:38:33.165 probably doesn't. NOTE Confidence: 0.9498266 00:38:34.505 --> 00:38:35.625 So this is my summary NOTE Confidence: 0.9498266 00:38:35.625 --> 00:38:37.145 of radioligand therapy. And by NOTE Confidence: 0.9498266 00:38:37.145 --> 00:38:38.105 the way, this is a NOTE Confidence: 0.9498266 00:38:38.105 --> 00:38:39.225 very odd area for drug NOTE Confidence: 0.9498266 00:38:39.225 --> 00:38:41.065 development. People are very, very NOTE Confidence: 0.9498266 00:38:41.065 --> 00:38:42.960 interested in replicating this. Because NOTE Confidence: 0.9498266 00:38:42.960 --> 00:38:43.920 right now, it's just two NOTE Confidence: 0.9498266 00:38:43.920 --> 00:38:45.219 diseases where RLTs NOTE Confidence: 0.9625311 00:38:45.520 --> 00:38:47.119 are actually approved. One is NOTE Confidence: 0.9625311 00:38:47.119 --> 00:38:48.400 prostate cancer like I showed NOTE Confidence: 0.9625311 00:38:48.400 --> 00:38:49.359 you, and the other is NOTE Confidence: 0.9625311 00:38:49.359 --> 00:38:49.859 neuroendocrine NOTE Confidence: 0.97157437 00:38:50.160 --> 00:38:52.080 tumors, okay, which are even NOTE Confidence: 0.97157437 00:38:52.080 --> 00:38:53.359 less common. But people are NOTE Confidence: 0.97157437 00:38:53.359 --> 00:38:54.640 very interested in this type NOTE Confidence: 0.97157437 00:38:54.640 --> 00:38:56.415 of approach in in bladder NOTE Confidence: 0.97157437 00:38:56.415 --> 00:38:57.775 cancer, breast cancer, and lung NOTE Confidence: 0.97157437 00:38:57.775 --> 00:38:59.215 cancer. And I think the NOTE Confidence: 0.97157437 00:38:59.215 --> 00:39:00.575 the ability to deliver this NOTE Confidence: 0.97157437 00:39:00.575 --> 00:39:01.395 type of radiopharmaceutical NOTE Confidence: 0.994036 00:39:01.855 --> 00:39:03.375 treatment, I think, will hinge NOTE Confidence: 0.994036 00:39:03.375 --> 00:39:04.575 on how good those targets NOTE Confidence: 0.994036 00:39:04.575 --> 00:39:05.535 are. We happen to have NOTE Confidence: 0.994036 00:39:05.535 --> 00:39:06.575 a really good target with NOTE Confidence: 0.994036 00:39:06.575 --> 00:39:08.355 prostate cancer, which is PSMA. NOTE Confidence: 0.9993288 00:39:08.895 --> 00:39:10.015 The other interesting thing that NOTE Confidence: 0.9993288 00:39:10.015 --> 00:39:11.640 you'll hear about is alpha NOTE Confidence: 0.9993288 00:39:11.640 --> 00:39:12.140 particles. NOTE Confidence: 0.9954801 00:39:12.520 --> 00:39:13.559 So, you know, I'm not NOTE Confidence: 0.9954801 00:39:13.559 --> 00:39:14.380 a physicist, NOTE Confidence: 0.9781553 00:39:15.079 --> 00:39:16.760 but there are better ways NOTE Confidence: 0.9781553 00:39:16.760 --> 00:39:18.539 of delivering a lethal dose NOTE Confidence: 0.9781553 00:39:18.680 --> 00:39:19.160 of, NOTE Confidence: 0.9754889 00:39:19.480 --> 00:39:20.460 of, radiopharmaceutical NOTE Confidence: 0.9981989 00:39:21.160 --> 00:39:22.599 that are more able to NOTE Confidence: 0.9981989 00:39:22.599 --> 00:39:24.280 kill these cancer cells with NOTE Confidence: 0.9981989 00:39:24.280 --> 00:39:25.099 less toxicity. NOTE Confidence: 0.9885278 00:39:26.445 --> 00:39:27.485 Okay. So the last part NOTE Confidence: 0.9885278 00:39:27.485 --> 00:39:28.205 of my talk is really NOTE Confidence: 0.9885278 00:39:28.205 --> 00:39:30.125 about immunotherapy. And, you know, NOTE Confidence: 0.9885278 00:39:30.125 --> 00:39:31.165 this was it's hard to NOTE Confidence: 0.9885278 00:39:31.165 --> 00:39:32.605 believe it's this was the NOTE Confidence: 0.9885278 00:39:32.605 --> 00:39:33.565 breakthrough of the year in NOTE Confidence: 0.9885278 00:39:33.565 --> 00:39:34.765 two thousand thirteen. So we've NOTE Confidence: 0.9885278 00:39:34.765 --> 00:39:35.645 been living with this now NOTE Confidence: 0.9885278 00:39:35.645 --> 00:39:37.745 for almost a dozen years. NOTE Confidence: 0.9778967 00:39:38.125 --> 00:39:39.400 And, of course, you know, NOTE Confidence: 0.9778967 00:39:39.400 --> 00:39:40.780 lung cancer is the prototypical, NOTE Confidence: 0.994563 00:39:41.239 --> 00:39:41.739 disease, NOTE Confidence: 0.97722435 00:39:42.840 --> 00:39:44.600 along with melanoma and and NOTE Confidence: 0.97722435 00:39:44.600 --> 00:39:46.840 kidney cancer where immunotherapies made, NOTE Confidence: 0.97722435 00:39:47.160 --> 00:39:48.060 important differences. NOTE Confidence: 0.9821022 00:39:48.520 --> 00:39:50.440 But prostate cancer actually was NOTE Confidence: 0.9821022 00:39:50.440 --> 00:39:51.400 one of the first diseases NOTE Confidence: 0.9821022 00:39:51.400 --> 00:39:52.920 where a checkpoint inhibitor was NOTE Confidence: 0.9821022 00:39:52.920 --> 00:39:54.620 tested. This was CTLA four. NOTE Confidence: 0.9821022 00:39:54.840 --> 00:39:55.985 And you can actually see NOTE Confidence: 0.9821022 00:39:55.985 --> 00:39:57.525 that there was a suggestion NOTE Confidence: 0.9821022 00:39:57.665 --> 00:39:59.105 that some patients might benefit NOTE Confidence: 0.9821022 00:39:59.105 --> 00:40:00.545 from a checkpoint inhibitor even NOTE Confidence: 0.9821022 00:40:00.545 --> 00:40:01.665 in prostate cancer, but it NOTE Confidence: 0.9821022 00:40:01.665 --> 00:40:02.864 was never developed further. This NOTE Confidence: 0.9821022 00:40:02.864 --> 00:40:03.364 was, NOTE Confidence: 0.99587077 00:40:03.905 --> 00:40:04.405 predating, NOTE Confidence: 0.9302025 00:40:04.785 --> 00:40:05.825 the use of PD L NOTE Confidence: 0.9302025 00:40:05.825 --> 00:40:07.125 one or PD one inhibitors. NOTE Confidence: 0.98949695 00:40:07.630 --> 00:40:08.750 But there was a suggestion NOTE Confidence: 0.98949695 00:40:08.750 --> 00:40:09.950 that maybe some patients with NOTE Confidence: 0.98949695 00:40:09.950 --> 00:40:12.109 prostate cancer actually could benefit NOTE Confidence: 0.98949695 00:40:12.109 --> 00:40:13.790 from checkpoint inhibitors. But in NOTE Confidence: 0.98949695 00:40:13.790 --> 00:40:14.369 the end, NOTE Confidence: 0.96710175 00:40:14.670 --> 00:40:16.109 the only approval for checkpoint NOTE Confidence: 0.96710175 00:40:16.109 --> 00:40:17.710 inhibitors in prostate cancer right NOTE Confidence: 0.96710175 00:40:17.710 --> 00:40:19.230 now are in TMB high NOTE Confidence: 0.96710175 00:40:19.230 --> 00:40:20.530 or MSI high tumors, NOTE Confidence: 0.9627871 00:40:21.005 --> 00:40:22.045 which, as you know, are NOTE Confidence: 0.9627871 00:40:22.045 --> 00:40:23.965 highly mutated prostate cancer. Prostate NOTE Confidence: 0.9627871 00:40:23.965 --> 00:40:25.085 cancers in general are not NOTE Confidence: 0.9627871 00:40:25.085 --> 00:40:25.985 highly mutated. NOTE Confidence: 0.9725934 00:40:27.725 --> 00:40:28.925 The prevalence is probably around NOTE Confidence: 0.9725934 00:40:28.925 --> 00:40:29.985 three to five percent, NOTE Confidence: 0.9785045 00:40:30.285 --> 00:40:31.245 and the rate of response NOTE Confidence: 0.9785045 00:40:31.245 --> 00:40:32.925 is about fifty percent, but NOTE Confidence: 0.9785045 00:40:32.925 --> 00:40:34.045 some of these are durable. NOTE Confidence: 0.9785045 00:40:34.045 --> 00:40:35.219 You can't really see the NOTE Confidence: 0.9785045 00:40:35.219 --> 00:40:36.260 the bottom there. But the NOTE Confidence: 0.9785045 00:40:36.260 --> 00:40:36.760 progression NOTE Confidence: 0.97978526 00:40:37.060 --> 00:40:38.500 free survival for those with NOTE Confidence: 0.97978526 00:40:38.500 --> 00:40:40.180 very high TMBs, you can NOTE Confidence: 0.97978526 00:40:40.180 --> 00:40:41.700 see from from upper to NOTE Confidence: 0.97978526 00:40:41.700 --> 00:40:43.619 lower, the highest TMBs. You NOTE Confidence: 0.97978526 00:40:43.619 --> 00:40:45.060 can see that they're, they NOTE Confidence: 0.97978526 00:40:45.060 --> 00:40:46.820 they are not progressing after NOTE Confidence: 0.97978526 00:40:46.820 --> 00:40:47.700 two or three years, some NOTE Confidence: 0.97978526 00:40:47.700 --> 00:40:49.140 of these patients. So, again, NOTE Confidence: 0.97978526 00:40:49.140 --> 00:40:50.680 it behooves us to check, NOTE Confidence: 0.9655806 00:40:51.045 --> 00:40:52.724 for for evidence of a NOTE Confidence: 0.9655806 00:40:52.724 --> 00:40:54.665 tumor mutational burden or MSI NOTE Confidence: 0.9655806 00:40:54.805 --> 00:40:56.585 high or unstable disease. NOTE Confidence: 0.98573303 00:40:58.005 --> 00:40:59.525 But I think the real NOTE Confidence: 0.98573303 00:40:59.765 --> 00:41:00.645 you know, that's a very NOTE Confidence: 0.98573303 00:41:00.645 --> 00:41:01.925 small percentage of patients. So, NOTE Confidence: 0.98573303 00:41:01.925 --> 00:41:02.885 you know, I I probably NOTE Confidence: 0.98573303 00:41:02.885 --> 00:41:03.844 have seen one or two, NOTE Confidence: 0.98573303 00:41:03.844 --> 00:41:04.645 even though I have a NOTE Confidence: 0.98573303 00:41:04.645 --> 00:41:05.625 very big practice, NOTE Confidence: 0.98627365 00:41:06.759 --> 00:41:08.200 is is really taking a NOTE Confidence: 0.98627365 00:41:08.200 --> 00:41:09.000 a page out of the NOTE Confidence: 0.98627365 00:41:09.000 --> 00:41:11.000 PSMA handbook and to look NOTE Confidence: 0.98627365 00:41:11.000 --> 00:41:11.239 at, NOTE Confidence: 0.93054616 00:41:11.880 --> 00:41:13.420 bispecific t cell engagers, NOTE Confidence: 0.97801447 00:41:13.719 --> 00:41:15.719 so called BiTE. So remember, NOTE Confidence: 0.97801447 00:41:15.719 --> 00:41:16.599 if you have a target NOTE Confidence: 0.97801447 00:41:16.599 --> 00:41:17.719 and now you can deliver NOTE Confidence: 0.97801447 00:41:17.719 --> 00:41:18.299 a radiopharmaceutical, NOTE Confidence: 0.95636624 00:41:18.759 --> 00:41:19.880 maybe you can deliver other NOTE Confidence: 0.95636624 00:41:19.880 --> 00:41:21.864 things like T cells. We NOTE Confidence: 0.95636624 00:41:21.864 --> 00:41:22.664 know that T cells are NOTE Confidence: 0.95636624 00:41:22.664 --> 00:41:23.964 the things that kill cancer. NOTE Confidence: 0.95636624 00:41:24.025 --> 00:41:25.625 Right? Why don't they work NOTE Confidence: 0.95636624 00:41:25.625 --> 00:41:26.984 in can prostate cancer in NOTE Confidence: 0.95636624 00:41:26.984 --> 00:41:28.025 general like in these, NOTE Confidence: 0.99427146 00:41:28.585 --> 00:41:30.184 in this curve? Well, probably NOTE Confidence: 0.99427146 00:41:30.184 --> 00:41:30.984 because they don't know where NOTE Confidence: 0.99427146 00:41:30.984 --> 00:41:31.864 to go. So if you NOTE Confidence: 0.99427146 00:41:31.864 --> 00:41:33.224 can be smart and deliver NOTE Confidence: 0.99427146 00:41:33.224 --> 00:41:34.265 the T cell directly to NOTE Confidence: 0.99427146 00:41:34.265 --> 00:41:35.545 the cancer cell, maybe you'll NOTE Confidence: 0.99427146 00:41:35.545 --> 00:41:36.239 have a better, NOTE Confidence: 0.9734508 00:41:36.960 --> 00:41:37.940 out outcome. NOTE Confidence: 0.99114984 00:41:38.800 --> 00:41:39.760 So this was one of NOTE Confidence: 0.99114984 00:41:39.760 --> 00:41:40.960 the first bites that certainly NOTE Confidence: 0.99114984 00:41:40.960 --> 00:41:41.920 got a lot of attention. NOTE Confidence: 0.9847371 00:41:42.239 --> 00:41:43.280 This was now five years NOTE Confidence: 0.9847371 00:41:43.280 --> 00:41:43.780 ago. NOTE Confidence: 0.93856615 00:41:44.160 --> 00:41:44.960 And you can see that NOTE Confidence: 0.93856615 00:41:44.960 --> 00:41:45.619 a majority NOTE Confidence: 0.98871017 00:41:46.080 --> 00:41:47.600 of patients receiving AMG one NOTE Confidence: 0.98871017 00:41:47.600 --> 00:41:49.219 sixty, which was a PSMA NOTE Confidence: 0.98871017 00:41:49.360 --> 00:41:49.860 directed, NOTE Confidence: 0.9837439 00:41:50.320 --> 00:41:52.205 bispecific t t cell engager, NOTE Confidence: 0.9837439 00:41:52.425 --> 00:41:53.785 actually had a PSA response NOTE Confidence: 0.9837439 00:41:53.785 --> 00:41:55.465 in this waterfall plot. It NOTE Confidence: 0.9837439 00:41:55.465 --> 00:41:56.985 had some toxicities that really NOTE Confidence: 0.9837439 00:41:56.985 --> 00:41:57.965 killed this drug, NOTE Confidence: 0.9842794 00:41:58.265 --> 00:41:59.465 but there was this, you NOTE Confidence: 0.9842794 00:41:59.465 --> 00:42:00.265 know, there are a bunch NOTE Confidence: 0.9842794 00:42:00.265 --> 00:42:01.225 of other ones that I NOTE Confidence: 0.9842794 00:42:01.225 --> 00:42:02.105 showed you on that first NOTE Confidence: 0.9842794 00:42:02.105 --> 00:42:03.625 slide. And this was, this NOTE Confidence: 0.9842794 00:42:03.625 --> 00:42:04.905 is also something that is NOTE Confidence: 0.9842794 00:42:04.905 --> 00:42:06.710 quite, I think, exciting and NOTE Confidence: 0.9842794 00:42:06.710 --> 00:42:08.469 interesting, but I think it NOTE Confidence: 0.9842794 00:42:08.469 --> 00:42:09.750 reminds us of the toxicity. NOTE Confidence: 0.9842794 00:42:09.750 --> 00:42:10.789 You know, it's interesting. We'll NOTE Confidence: 0.9842794 00:42:10.789 --> 00:42:12.170 see the same drug used NOTE Confidence: 0.9842794 00:42:12.230 --> 00:42:13.510 in breast cancer and lung NOTE Confidence: 0.9842794 00:42:13.510 --> 00:42:15.109 cancer and prostate cancer, and NOTE Confidence: 0.9842794 00:42:15.109 --> 00:42:16.469 sometimes we'll see more toxicity NOTE Confidence: 0.9842794 00:42:16.469 --> 00:42:18.069 in prostate cancer patients. I NOTE Confidence: 0.9842794 00:42:18.069 --> 00:42:19.875 don't always understand why. I NOTE Confidence: 0.9842794 00:42:19.875 --> 00:42:20.835 have a theory about it, NOTE Confidence: 0.9842794 00:42:20.835 --> 00:42:22.535 which relates to androgen deprivation, NOTE Confidence: 0.9842794 00:42:22.675 --> 00:42:24.114 but we do see more NOTE Confidence: 0.9842794 00:42:24.114 --> 00:42:25.875 toxicity in prostate cancer patients NOTE Confidence: 0.9842794 00:42:25.875 --> 00:42:27.315 than we might sometimes expect NOTE Confidence: 0.9842794 00:42:27.315 --> 00:42:28.375 with the same drug. NOTE Confidence: 0.95028466 00:42:28.675 --> 00:42:29.815 But this is a combination NOTE Confidence: 0.95028466 00:42:29.875 --> 00:42:31.175 of a a a bispecific NOTE Confidence: 0.95028466 00:42:31.395 --> 00:42:32.135 from Regeneron NOTE Confidence: 0.9095829 00:42:32.835 --> 00:42:34.215 that, again, shows NOTE Confidence: 0.99973446 00:42:34.560 --> 00:42:35.060 significant NOTE Confidence: 0.97368515 00:42:35.680 --> 00:42:36.960 responses, especially when combined with NOTE Confidence: 0.97368515 00:42:36.960 --> 00:42:38.480 the checkpoint inhibitor. But it NOTE Confidence: 0.97368515 00:42:38.480 --> 00:42:39.600 was toxic, and there were NOTE Confidence: 0.97368515 00:42:39.600 --> 00:42:40.800 several deaths. So what they've NOTE Confidence: 0.97368515 00:42:40.800 --> 00:42:41.840 done is they've taken away NOTE Confidence: 0.97368515 00:42:41.840 --> 00:42:43.040 the checkpoint inhibitor, and they're NOTE Confidence: 0.97368515 00:42:43.040 --> 00:42:45.460 just using the bispecific alone. NOTE Confidence: 0.98599774 00:42:46.400 --> 00:42:47.520 And this got a lot NOTE Confidence: 0.98599774 00:42:47.520 --> 00:42:48.900 of attention last year, NOTE Confidence: 0.83659667 00:42:49.395 --> 00:42:50.775 a couple years ago now, NOTE Confidence: 0.84403133 00:42:51.155 --> 00:42:52.614 a STEEP one bispecific. NOTE Confidence: 0.9930068 00:42:53.075 --> 00:42:54.535 STEEP one is another target, NOTE Confidence: 0.86625594 00:42:55.315 --> 00:42:56.855 immune target that, NOTE Confidence: 0.94426715 00:42:57.155 --> 00:42:58.675 showed almost a sixty percent NOTE Confidence: 0.94426715 00:42:58.675 --> 00:43:00.114 response rate. Again, in highly NOTE Confidence: 0.94426715 00:43:00.114 --> 00:43:01.315 pretreated patients, and you can NOTE Confidence: 0.94426715 00:43:01.315 --> 00:43:02.594 see the majority of patients NOTE Confidence: 0.94426715 00:43:02.594 --> 00:43:03.094 responded. NOTE Confidence: 0.9992527 00:43:03.690 --> 00:43:05.150 So I think this concept NOTE Confidence: 0.9977912 00:43:05.530 --> 00:43:06.030 has, NOTE Confidence: 0.97449535 00:43:06.730 --> 00:43:08.329 has, legs. I think we NOTE Confidence: 0.97449535 00:43:08.329 --> 00:43:09.609 really know that we can NOTE Confidence: 0.97449535 00:43:09.609 --> 00:43:10.650 deliver a t cell to NOTE Confidence: 0.97449535 00:43:10.650 --> 00:43:11.609 the site of cancer as NOTE Confidence: 0.97449535 00:43:11.609 --> 00:43:12.650 long as we can control NOTE Confidence: 0.97449535 00:43:12.650 --> 00:43:13.310 the toxicity. NOTE Confidence: 0.991265 00:43:14.969 --> 00:43:16.010 And the last point I NOTE Confidence: 0.991265 00:43:16.010 --> 00:43:17.369 would make is really around, NOTE Confidence: 0.991265 00:43:17.609 --> 00:43:18.570 what we know to be NOTE Confidence: 0.991265 00:43:18.570 --> 00:43:19.070 a NOTE Confidence: 0.9689853 00:43:19.575 --> 00:43:20.855 a pathway of progression for NOTE Confidence: 0.9689853 00:43:20.855 --> 00:43:22.395 prostate cancer, and that's neuroendocrine NOTE Confidence: 0.9689853 00:43:22.535 --> 00:43:23.035 differentiation. NOTE Confidence: 0.9893975 00:43:23.815 --> 00:43:24.715 This is a, NOTE Confidence: 0.98089325 00:43:25.175 --> 00:43:26.855 a cartoon that talks about NOTE Confidence: 0.98089325 00:43:26.855 --> 00:43:28.055 kind of the progression from NOTE Confidence: 0.98089325 00:43:28.055 --> 00:43:28.855 the left to the right NOTE Confidence: 0.98089325 00:43:28.855 --> 00:43:30.474 of a normal prostate gland NOTE Confidence: 0.98089325 00:43:30.535 --> 00:43:31.594 to typical adenocarcinoma. NOTE Confidence: 0.9995662 00:43:32.055 --> 00:43:33.594 Those are the PSA producing NOTE Confidence: 0.9880521 00:43:34.210 --> 00:43:35.489 prostate cancer cells that might NOTE Confidence: 0.9880521 00:43:35.489 --> 00:43:36.850 spread to the bone, and NOTE Confidence: 0.9880521 00:43:36.850 --> 00:43:38.290 it moves into this so NOTE Confidence: 0.9880521 00:43:38.290 --> 00:43:39.030 called neuroendocrine, NOTE Confidence: 0.98236513 00:43:40.450 --> 00:43:43.010 phenotype. Neuroendocrine tumor cells are NOTE Confidence: 0.98236513 00:43:43.090 --> 00:43:44.850 don't make PSA. They are NOTE Confidence: 0.98236513 00:43:44.850 --> 00:43:46.290 not as responsive to androgen. NOTE Confidence: 0.98236513 00:43:46.290 --> 00:43:47.090 And what you see by NOTE Confidence: 0.98236513 00:43:47.090 --> 00:43:48.224 the time they develop pure NOTE Confidence: 0.98236513 00:43:48.224 --> 00:43:49.825 neuroendocrine prostate cancer is that NOTE Confidence: 0.98236513 00:43:49.825 --> 00:43:51.505 these cancers may have unusual NOTE Confidence: 0.98236513 00:43:51.505 --> 00:43:52.625 patterns to spread. They may NOTE Confidence: 0.98236513 00:43:52.625 --> 00:43:53.744 go to the brain, which NOTE Confidence: 0.98236513 00:43:53.744 --> 00:43:55.344 almost never happens normally in NOTE Confidence: 0.98236513 00:43:55.344 --> 00:43:57.184 prostate cancer, and they're highly NOTE Confidence: 0.98236513 00:43:57.184 --> 00:43:58.144 aggressive. They may go to NOTE Confidence: 0.98236513 00:43:58.144 --> 00:43:59.204 the liver, for example. NOTE Confidence: 0.97958195 00:43:59.744 --> 00:44:01.619 And this has been, unfortunately, NOTE Confidence: 0.97958195 00:44:01.680 --> 00:44:02.800 a way in which our NOTE Confidence: 0.97958195 00:44:02.800 --> 00:44:04.400 ARPs and the other androgen NOTE Confidence: 0.97958195 00:44:04.400 --> 00:44:05.860 pathway drugs that we have NOTE Confidence: 0.91647375 00:44:06.239 --> 00:44:07.920 stop working, and these patients NOTE Confidence: 0.91647375 00:44:07.920 --> 00:44:09.860 may progress and chemotherapy, unfortunately, NOTE Confidence: 0.91647375 00:44:09.920 --> 00:44:11.619 has a very, modest effect. NOTE Confidence: 0.9613439 00:44:12.000 --> 00:44:12.880 Now this is something that NOTE Confidence: 0.9613439 00:44:12.880 --> 00:44:14.880 has broad implications across lots NOTE Confidence: 0.9613439 00:44:14.880 --> 00:44:16.175 of diseases because we know NOTE Confidence: 0.9613439 00:44:16.175 --> 00:44:18.495 actually that neuroendocrine carcinoma is, NOTE Confidence: 0.9613439 00:44:18.815 --> 00:44:20.114 present all over the body. NOTE Confidence: 0.9613439 00:44:20.175 --> 00:44:21.695 These neuroendocrine cells are present NOTE Confidence: 0.9613439 00:44:21.695 --> 00:44:22.735 all over the body. And NOTE Confidence: 0.9613439 00:44:22.735 --> 00:44:24.015 in fact, you know, probably NOTE Confidence: 0.9613439 00:44:24.015 --> 00:44:25.535 the neuroendocrine type of cancer NOTE Confidence: 0.9613439 00:44:25.535 --> 00:44:26.415 that we know the most NOTE Confidence: 0.9613439 00:44:26.415 --> 00:44:27.510 about is in the lung. NOTE Confidence: 0.9613439 00:44:27.670 --> 00:44:28.230 And so a lot of NOTE Confidence: 0.9613439 00:44:28.230 --> 00:44:29.030 the things we've done for NOTE Confidence: 0.9613439 00:44:29.030 --> 00:44:30.950 neuroendocrine pros can prostate cancer NOTE Confidence: 0.9613439 00:44:30.950 --> 00:44:32.469 has come from our understanding NOTE Confidence: 0.9613439 00:44:32.469 --> 00:44:33.670 of how lung cancer doctors NOTE Confidence: 0.9613439 00:44:33.670 --> 00:44:34.410 treat neuroendocrine, NOTE Confidence: 0.9957207 00:44:35.190 --> 00:44:36.650 cancer or small cell cancers. NOTE Confidence: 0.98041064 00:44:37.510 --> 00:44:38.469 But there is a target NOTE Confidence: 0.98041064 00:44:38.469 --> 00:44:39.750 here too called DLL three NOTE Confidence: 0.98041064 00:44:39.750 --> 00:44:42.305 or delta like ligand, three. NOTE Confidence: 0.98041064 00:44:42.364 --> 00:44:43.244 And you can see here NOTE Confidence: 0.98041064 00:44:43.244 --> 00:44:44.205 that if you look at, NOTE Confidence: 0.98041064 00:44:44.445 --> 00:44:45.984 staining for DLL three, NOTE Confidence: 0.99812317 00:44:46.364 --> 00:44:47.244 which is in the last NOTE Confidence: 0.99812317 00:44:47.244 --> 00:44:47.744 panel, NOTE Confidence: 0.9428803 00:44:48.205 --> 00:44:49.484 you can see that, about NOTE Confidence: 0.9428803 00:44:49.484 --> 00:44:51.244 seventy six percent of, advanced NOTE Confidence: 0.9428803 00:44:51.244 --> 00:44:53.505 prostate cancers, neuroendocrine prostate cancers NOTE Confidence: 0.9428803 00:44:53.565 --> 00:44:55.680 express d DLL three, and NOTE Confidence: 0.9428803 00:44:55.680 --> 00:44:56.880 they don't express the AR. NOTE Confidence: 0.9428803 00:44:56.880 --> 00:44:58.319 They lose AR expression. They NOTE Confidence: 0.9428803 00:44:58.319 --> 00:45:00.319 express DLL three. So last NOTE Confidence: 0.9428803 00:45:00.319 --> 00:45:01.440 year, there was a new NOTE Confidence: 0.9428803 00:45:01.440 --> 00:45:03.200 BiTE that was approved for NOTE Confidence: 0.9428803 00:45:03.200 --> 00:45:04.819 small cell lung cancer called NOTE Confidence: 0.9428803 00:45:04.880 --> 00:45:05.380 tarlatanib NOTE Confidence: 0.66512287 00:45:06.160 --> 00:45:06.819 or tarlatanib. NOTE Confidence: 0.9978492 00:45:07.855 --> 00:45:08.355 And, NOTE Confidence: 0.9199454 00:45:08.655 --> 00:45:09.614 this is a you can NOTE Confidence: 0.9199454 00:45:09.614 --> 00:45:11.215 see they are targeted towards, NOTE Confidence: 0.98017275 00:45:11.614 --> 00:45:13.155 delivering a t cell directly NOTE Confidence: 0.98017275 00:45:13.215 --> 00:45:14.255 to a, NOTE Confidence: 0.98175883 00:45:14.655 --> 00:45:16.175 small cell lung cancer that NOTE Confidence: 0.98175883 00:45:16.175 --> 00:45:17.855 might express DLL three. So NOTE Confidence: 0.98175883 00:45:17.855 --> 00:45:18.815 this has actually been looked NOTE Confidence: 0.98175883 00:45:18.815 --> 00:45:20.255 at in prostate cancer. And, NOTE Confidence: 0.98175883 00:45:20.255 --> 00:45:21.510 again, you can see that NOTE Confidence: 0.98175883 00:45:21.510 --> 00:45:22.870 in patients who have DLL NOTE Confidence: 0.98175883 00:45:22.870 --> 00:45:24.950 three positive neuroendocrine prostate cancer NOTE Confidence: 0.98175883 00:45:24.950 --> 00:45:25.830 that there are some long NOTE Confidence: 0.98175883 00:45:25.830 --> 00:45:26.650 term responders. NOTE Confidence: 0.9813532 00:45:26.950 --> 00:45:28.070 Overall, the response rate was NOTE Confidence: 0.9813532 00:45:28.070 --> 00:45:29.270 only ten percent, but I NOTE Confidence: 0.9813532 00:45:29.270 --> 00:45:30.390 think this again gets to NOTE Confidence: 0.9813532 00:45:30.390 --> 00:45:31.350 the idea that we have NOTE Confidence: 0.9813532 00:45:31.350 --> 00:45:32.790 to find and target the NOTE Confidence: 0.9813532 00:45:32.790 --> 00:45:33.450 right patients. NOTE Confidence: 0.91616446 00:45:34.755 --> 00:45:35.954 So these are my last NOTE Confidence: 0.91616446 00:45:35.954 --> 00:45:37.015 couple of slides. NOTE Confidence: 0.9915829 00:45:37.795 --> 00:45:39.635 Targeted therapy for prostate cancer, NOTE Confidence: 0.9915829 00:45:39.635 --> 00:45:40.755 I think we're seeing it. NOTE Confidence: 0.9915829 00:45:40.755 --> 00:45:42.135 AR is the first target, NOTE Confidence: 0.9915829 00:45:42.194 --> 00:45:43.734 but we have PARP inhibitors NOTE Confidence: 0.9915829 00:45:43.795 --> 00:45:45.015 for DDR mutations. NOTE Confidence: 0.95429343 00:45:45.395 --> 00:45:46.914 MSI high tumors should get, NOTE Confidence: 0.95429343 00:45:47.154 --> 00:45:48.989 checkpoint inhibitors. But we're seeing NOTE Confidence: 0.95429343 00:45:48.989 --> 00:45:51.170 these PSMA directed therapies, certainly NOTE Confidence: 0.94136167 00:45:51.469 --> 00:45:51.969 radioligand NOTE Confidence: 0.9439404 00:45:52.270 --> 00:45:53.330 therapies, but also, NOTE Confidence: 0.93855596 00:45:53.790 --> 00:45:54.530 these BiTEs. NOTE Confidence: 0.9882589 00:45:54.910 --> 00:45:56.190 And DLL three is a NOTE Confidence: 0.9882589 00:45:56.190 --> 00:45:58.350 promising target for neuroendocrine prostate NOTE Confidence: 0.9882589 00:45:58.350 --> 00:45:58.850 cancer. NOTE Confidence: 0.99522907 00:45:59.390 --> 00:46:00.590 So I'm gonna end on NOTE Confidence: 0.99522907 00:46:00.590 --> 00:46:01.875 the concept that I I NOTE Confidence: 0.99522907 00:46:01.955 --> 00:46:02.855 came here for NOTE Confidence: 0.943881 00:46:03.155 --> 00:46:04.675 to Yale, which is how NOTE Confidence: 0.943881 00:46:04.675 --> 00:46:05.955 are we gonna use precision NOTE Confidence: 0.943881 00:46:05.955 --> 00:46:07.475 medicine more accurately? Here's one NOTE Confidence: 0.943881 00:46:07.475 --> 00:46:08.775 disease, a big disease, NOTE Confidence: 0.964287 00:46:09.075 --> 00:46:10.315 that is still lethal for NOTE Confidence: 0.964287 00:46:10.315 --> 00:46:11.795 a subset of patients. How NOTE Confidence: 0.964287 00:46:11.795 --> 00:46:12.995 do we take what we NOTE Confidence: 0.964287 00:46:12.995 --> 00:46:14.195 learn about the patient? And NOTE Confidence: 0.964287 00:46:14.195 --> 00:46:15.475 you can see, this is NOTE Confidence: 0.964287 00:46:15.475 --> 00:46:17.075 from an AACR report. But, NOTE Confidence: 0.964287 00:46:17.075 --> 00:46:17.575 basically, NOTE Confidence: 0.994311 00:46:17.930 --> 00:46:18.970 think about the world we NOTE Confidence: 0.994311 00:46:18.970 --> 00:46:20.090 live in. We're not just NOTE Confidence: 0.994311 00:46:20.410 --> 00:46:21.930 these are not men who NOTE Confidence: 0.994311 00:46:21.930 --> 00:46:22.810 just come in with one NOTE Confidence: 0.994311 00:46:22.810 --> 00:46:24.090 disease. They come in with NOTE Confidence: 0.994311 00:46:24.090 --> 00:46:26.090 a background of genetics and NOTE Confidence: 0.994311 00:46:26.090 --> 00:46:28.410 and lifestyle factors and and NOTE Confidence: 0.994311 00:46:28.410 --> 00:46:29.930 the epigenome and how they NOTE Confidence: 0.994311 00:46:29.930 --> 00:46:31.305 present. And there's so many NOTE Confidence: 0.994311 00:46:31.305 --> 00:46:32.585 factors that we don't account NOTE Confidence: 0.994311 00:46:32.585 --> 00:46:33.864 for when we try to NOTE Confidence: 0.994311 00:46:33.864 --> 00:46:34.364 deliver NOTE Confidence: 0.9890919 00:46:34.744 --> 00:46:35.785 the right treatment to each NOTE Confidence: 0.9890919 00:46:35.785 --> 00:46:37.145 of these patients. And I'm NOTE Confidence: 0.9890919 00:46:37.145 --> 00:46:38.364 not saying that we can NOTE Confidence: 0.9890919 00:46:38.505 --> 00:46:39.545 account for all this, but, NOTE Confidence: 0.9890919 00:46:39.545 --> 00:46:40.665 you know, we can definitely NOTE Confidence: 0.9890919 00:46:40.665 --> 00:46:41.964 put people into categories NOTE Confidence: 0.9804376 00:46:42.585 --> 00:46:43.864 that better account for some NOTE Confidence: 0.9804376 00:46:43.864 --> 00:46:44.984 of these factors that right NOTE Confidence: 0.9804376 00:46:44.984 --> 00:46:46.185 now we're not measuring at NOTE Confidence: 0.9804376 00:46:46.185 --> 00:46:46.560 all. NOTE Confidence: 0.98095703 00:46:47.600 --> 00:46:48.800 And I think that AI NOTE Confidence: 0.98095703 00:46:48.800 --> 00:46:49.840 is an area where we're NOTE Confidence: 0.98095703 00:46:49.840 --> 00:46:51.360 gonna learn more about how NOTE Confidence: 0.98095703 00:46:51.360 --> 00:46:52.719 to bring this information together. NOTE Confidence: 0.98095703 00:46:52.719 --> 00:46:53.360 This is what I was NOTE Confidence: 0.98095703 00:46:53.360 --> 00:46:54.660 trying to do at Sema4 NOTE Confidence: 0.98095703 00:46:54.719 --> 00:46:55.760 when I was there and NOTE Confidence: 0.98095703 00:46:55.760 --> 00:46:56.560 what I think we can NOTE Confidence: 0.98095703 00:46:56.560 --> 00:46:58.080 do here with with, the NOTE Confidence: 0.98095703 00:46:58.080 --> 00:46:58.580 multidisciplinary NOTE Confidence: 0.9620035 00:46:59.040 --> 00:47:00.984 excellence we have in pathology, NOTE Confidence: 0.9620035 00:47:00.984 --> 00:47:01.484 molecular, NOTE Confidence: 0.99427783 00:47:02.185 --> 00:47:02.685 genetics, NOTE Confidence: 0.9882543 00:47:03.145 --> 00:47:04.285 with, bioinformatics, NOTE Confidence: 0.98868674 00:47:04.585 --> 00:47:05.565 etcetera. So, NOTE Confidence: 0.98535377 00:47:06.425 --> 00:47:07.705 you know, this paper came NOTE Confidence: 0.98535377 00:47:07.705 --> 00:47:08.665 out a few years ago NOTE Confidence: 0.98535377 00:47:08.665 --> 00:47:10.984 where multimodal AI, which is NOTE Confidence: 0.98535377 00:47:10.984 --> 00:47:12.744 really using a combination of NOTE Confidence: 0.98535377 00:47:12.744 --> 00:47:13.244 histology NOTE Confidence: 0.98725873 00:47:14.170 --> 00:47:15.930 plus clinical data from they NOTE Confidence: 0.98725873 00:47:15.930 --> 00:47:18.110 used, multiple randomized clinical trials. NOTE Confidence: 0.98725873 00:47:18.170 --> 00:47:19.710 They created an AI score NOTE Confidence: 0.9655331 00:47:20.570 --> 00:47:22.730 and, basically predicted the outcomes NOTE Confidence: 0.9655331 00:47:22.730 --> 00:47:23.930 of of patients. And they NOTE Confidence: 0.9655331 00:47:23.930 --> 00:47:24.989 actually reclassified, NOTE Confidence: 0.998721 00:47:26.170 --> 00:47:27.630 forty two percent of patients NOTE Confidence: 0.87890077 00:47:28.194 --> 00:47:29.875 compared to clinical risk factors NOTE Confidence: 0.87890077 00:47:29.875 --> 00:47:31.335 was was so called NCCN NOTE Confidence: 0.87890077 00:47:31.395 --> 00:47:31.895 criteria. NOTE Confidence: 0.9889486 00:47:33.155 --> 00:47:34.515 In other words, they were NOTE Confidence: 0.9889486 00:47:34.515 --> 00:47:35.875 much more accurate for about NOTE Confidence: 0.9889486 00:47:35.875 --> 00:47:36.994 forty percent of the patients. NOTE Confidence: 0.9889486 00:47:36.994 --> 00:47:38.434 So we're making decisions based NOTE Confidence: 0.9889486 00:47:38.434 --> 00:47:39.875 on clinical factors that I NOTE Confidence: 0.9889486 00:47:39.875 --> 00:47:41.395 mentioned earlier, like PSA and NOTE Confidence: 0.9889486 00:47:41.395 --> 00:47:41.895 staging. NOTE Confidence: 0.9997591 00:47:42.594 --> 00:47:43.255 And this NOTE Confidence: 0.99976254 00:47:43.710 --> 00:47:44.450 AI program NOTE Confidence: 0.9898837 00:47:44.750 --> 00:47:46.190 was so potent in predicting NOTE Confidence: 0.9898837 00:47:46.190 --> 00:47:47.550 this and is now commercially NOTE Confidence: 0.9898837 00:47:47.550 --> 00:47:48.750 available that it made it NOTE Confidence: 0.9898837 00:47:48.750 --> 00:47:50.349 into the NCCN guidelines this NOTE Confidence: 0.9898837 00:47:50.349 --> 00:47:50.849 year, NOTE Confidence: 0.9784646 00:47:51.550 --> 00:47:53.250 as a both a prognostic NOTE Confidence: 0.97989833 00:47:53.710 --> 00:47:55.390 tool, which, you know, has NOTE Confidence: 0.97989833 00:47:55.390 --> 00:47:56.805 limited value, but also as NOTE Confidence: 0.97989833 00:47:56.805 --> 00:47:57.844 a predictor of who should NOTE Confidence: 0.97989833 00:47:57.844 --> 00:47:59.464 get hormonal therapy with radiation. NOTE Confidence: 0.9830035 00:48:00.085 --> 00:48:01.285 So I'm just using this NOTE Confidence: 0.9830035 00:48:01.285 --> 00:48:02.565 as an example of where NOTE Confidence: 0.9830035 00:48:02.565 --> 00:48:04.005 we're gonna go in the NOTE Confidence: 0.9830035 00:48:04.005 --> 00:48:05.925 future as we as large NOTE Confidence: 0.9830035 00:48:05.925 --> 00:48:07.785 language models and and information NOTE Confidence: 0.9830035 00:48:08.005 --> 00:48:10.140 gets distilled into, bite sized NOTE Confidence: 0.9830035 00:48:10.140 --> 00:48:11.500 pieces that we as clinicians NOTE Confidence: 0.9830035 00:48:11.500 --> 00:48:12.859 can use, and I'm really NOTE Confidence: 0.9830035 00:48:12.859 --> 00:48:14.059 excited to to be part NOTE Confidence: 0.9830035 00:48:14.059 --> 00:48:15.260 of that. So I'll stop NOTE Confidence: 0.9830035 00:48:15.260 --> 00:48:16.219 there. Thank you very much NOTE Confidence: 0.9830035 00:48:16.219 --> 00:48:17.040 for your attention. NOTE Confidence: 0.68643755 00:48:21.260 --> 00:48:22.059 Thank you. I have time NOTE Confidence: 0.68643755 00:48:22.059 --> 00:48:22.719 for questions, NOTE Confidence: 0.9416778 00:48:23.579 --> 00:48:24.079 comments. NOTE Confidence: 0.93689275 00:48:25.625 --> 00:48:27.224 The floor is open. I'll NOTE Confidence: 0.93689275 00:48:27.224 --> 00:48:28.984 walk the microphone. Doctor Joseph NOTE Confidence: 0.93689275 00:48:28.984 --> 00:48:30.185 Kim, and then you can NOTE Confidence: 0.93689275 00:48:30.185 --> 00:48:31.145 keep the microphone and help NOTE Confidence: 0.93689275 00:48:31.145 --> 00:48:32.905 me. Okay. Thank you. Thank NOTE Confidence: 0.93689275 00:48:32.905 --> 00:48:33.864 you, William. This is a NOTE Confidence: 0.93689275 00:48:33.864 --> 00:48:36.265 fantastic talk. And, again, welcome NOTE Confidence: 0.93689275 00:48:36.265 --> 00:48:38.010 back, to Yale. So my NOTE Confidence: 0.93689275 00:48:38.010 --> 00:48:39.290 question I just wanna kinda NOTE Confidence: 0.93689275 00:48:39.290 --> 00:48:40.330 probe on the your last NOTE Confidence: 0.93689275 00:48:40.330 --> 00:48:41.690 point about the precision medicine NOTE Confidence: 0.93689275 00:48:41.690 --> 00:48:43.450 in prostate cancer. Again, in NOTE Confidence: 0.93689275 00:48:43.450 --> 00:48:44.410 prostate cancer, that may not NOTE Confidence: 0.93689275 00:48:44.410 --> 00:48:45.530 be the most precise term NOTE Confidence: 0.93689275 00:48:45.530 --> 00:48:46.570 either because we are still NOTE Confidence: 0.93689275 00:48:46.570 --> 00:48:47.930 learning how we define precision NOTE Confidence: 0.93689275 00:48:47.930 --> 00:48:49.695 oncology in prostate cancer. So, NOTE Confidence: 0.93689275 00:48:49.775 --> 00:48:50.655 you know, now as you NOTE Confidence: 0.93689275 00:48:50.655 --> 00:48:51.614 mentioned, we have a lot NOTE Confidence: 0.93689275 00:48:51.614 --> 00:48:52.815 of good treatment options available NOTE Confidence: 0.93689275 00:48:52.815 --> 00:48:54.255 for metastatic prostate cancer. You NOTE Confidence: 0.93689275 00:48:54.255 --> 00:48:56.675 mentioned novel AR integrator, RIP, NOTE Confidence: 0.9899231 00:48:56.975 --> 00:48:57.475 chemotherapy, NOTE Confidence: 0.83671045 00:48:58.415 --> 00:49:00.094 PSM target therapies, and PARP NOTE Confidence: 0.83671045 00:49:00.094 --> 00:49:00.594 inhibitors. NOTE Confidence: 0.9053772 00:49:01.375 --> 00:49:02.495 And doctor Roy Herbst, you NOTE Confidence: 0.9053772 00:49:02.495 --> 00:49:03.375 know, he when it was NOTE Confidence: 0.9053772 00:49:03.375 --> 00:49:05.010 a SWA, he's a SWA, NOTE Confidence: 0.9053772 00:49:05.010 --> 00:49:06.630 he designed this master protocol, NOTE Confidence: 0.93202615 00:49:07.010 --> 00:49:08.550 the master protocol, big umbrella NOTE Confidence: 0.93202615 00:49:08.610 --> 00:49:10.050 protocol. Are we as a NOTE Confidence: 0.93202615 00:49:10.050 --> 00:49:11.489 field in prostate cancer, are NOTE Confidence: 0.93202615 00:49:11.489 --> 00:49:12.770 we ready for things like NOTE Confidence: 0.93202615 00:49:12.770 --> 00:49:13.969 that? Because if you really NOTE Confidence: 0.93202615 00:49:13.969 --> 00:49:14.850 make an impact in in NOTE Confidence: 0.93202615 00:49:15.010 --> 00:49:16.075 clinical practice, practice, we have NOTE Confidence: 0.93202615 00:49:16.075 --> 00:49:16.795 to come up with a NOTE Confidence: 0.93202615 00:49:16.795 --> 00:49:18.415 good novel trial design. NOTE Confidence: 0.9902924 00:49:18.875 --> 00:49:19.675 I'd like to know what NOTE Confidence: 0.9902924 00:49:19.675 --> 00:49:20.955 your views on, on these NOTE Confidence: 0.9902924 00:49:20.955 --> 00:49:21.775 issues are. NOTE Confidence: 0.99734306 00:49:22.475 --> 00:49:23.435 Yeah. I mean, I think, NOTE Confidence: 0.99734306 00:49:23.675 --> 00:49:24.475 I would love to hear NOTE Confidence: 0.99734306 00:49:24.475 --> 00:49:25.835 Roy's thoughts too. NOTE Confidence: 0.9960669 00:49:26.795 --> 00:49:28.635 When we built this this NOTE Confidence: 0.9960669 00:49:28.635 --> 00:49:29.855 graphic, right, NOTE Confidence: 0.9959078 00:49:30.300 --> 00:49:31.360 that you can see, NOTE Confidence: 0.9772482 00:49:31.900 --> 00:49:32.860 we did it piece by NOTE Confidence: 0.9772482 00:49:32.860 --> 00:49:34.540 piece. It was certainly it NOTE Confidence: 0.9772482 00:49:34.540 --> 00:49:35.580 was painful, and it was NOTE Confidence: 0.9772482 00:49:35.580 --> 00:49:36.719 each clinical trial. NOTE Confidence: 0.9790394 00:49:37.020 --> 00:49:38.700 And the biggest problem with NOTE Confidence: 0.9790394 00:49:38.700 --> 00:49:40.380 this picture is we don't NOTE Confidence: 0.9790394 00:49:40.380 --> 00:49:41.260 know what we should do NOTE Confidence: 0.9790394 00:49:41.260 --> 00:49:42.620 when in which order. Right? NOTE Confidence: 0.9790394 00:49:42.620 --> 00:49:43.755 This is we have all NOTE Confidence: 0.9790394 00:49:43.755 --> 00:49:45.434 these debates about, sequencing of NOTE Confidence: 0.9790394 00:49:45.434 --> 00:49:45.934 treatments. NOTE Confidence: 0.9666212 00:49:46.635 --> 00:49:48.155 What you're suggesting is that NOTE Confidence: 0.9666212 00:49:48.155 --> 00:49:49.275 we move into this kind NOTE Confidence: 0.9666212 00:49:49.275 --> 00:49:51.114 of bigger thinking. Right? The NOTE Confidence: 0.9666212 00:49:51.275 --> 00:49:52.474 this idea of a an, NOTE Confidence: 0.9666212 00:49:52.875 --> 00:49:54.315 an umbrella protocol or a NOTE Confidence: 0.9666212 00:49:54.315 --> 00:49:56.075 protocol that's a master protocol NOTE Confidence: 0.9666212 00:49:56.075 --> 00:49:57.830 that that, accounts for all NOTE Confidence: 0.9666212 00:49:57.830 --> 00:49:58.890 of the different heterogeneity. NOTE Confidence: 0.988381 00:49:59.670 --> 00:50:00.950 The the the the real NOTE Confidence: 0.988381 00:50:00.950 --> 00:50:01.910 reason we haven't done it, NOTE Confidence: 0.988381 00:50:01.910 --> 00:50:03.110 as you know, Joseph, is NOTE Confidence: 0.988381 00:50:03.110 --> 00:50:04.469 that we don't have the NOTE Confidence: 0.988381 00:50:04.469 --> 00:50:06.489 categories for these patients. Right? NOTE Confidence: 0.9942464 00:50:06.790 --> 00:50:08.010 Most patients express NOTE Confidence: 0.99670446 00:50:08.310 --> 00:50:10.570 AR. Most patients express PSMA. NOTE Confidence: 0.9784398 00:50:11.625 --> 00:50:12.745 We don't know who responds NOTE Confidence: 0.9784398 00:50:12.745 --> 00:50:13.725 to, to, NOTE Confidence: 0.9954745 00:50:15.065 --> 00:50:16.344 chemotherapy. We don't know who NOTE Confidence: 0.9954745 00:50:16.344 --> 00:50:17.405 responds to, NOTE Confidence: 0.9460237 00:50:18.105 --> 00:50:18.605 to, NOTE Confidence: 0.99512607 00:50:19.385 --> 00:50:20.505 some of the treatments that NOTE Confidence: 0.99512607 00:50:20.505 --> 00:50:21.864 we give. So that is NOTE Confidence: 0.99512607 00:50:21.864 --> 00:50:22.825 the reason we don't have NOTE Confidence: 0.99512607 00:50:22.825 --> 00:50:24.120 this. The other thing that NOTE Confidence: 0.99512607 00:50:24.280 --> 00:50:25.960 maybe similar or different is NOTE Confidence: 0.99512607 00:50:25.960 --> 00:50:27.720 that these tumors evolve over NOTE Confidence: 0.99512607 00:50:27.720 --> 00:50:28.780 time. Right? NOTE Confidence: 0.9791921 00:50:29.560 --> 00:50:31.160 So, this picture shows that, NOTE Confidence: 0.9791921 00:50:31.160 --> 00:50:32.920 in fact, we induce some NOTE Confidence: 0.9791921 00:50:32.920 --> 00:50:34.440 of these resistance patterns. That's NOTE Confidence: 0.9791921 00:50:34.440 --> 00:50:35.720 not different from lung cancer. NOTE Confidence: 0.9791921 00:50:35.720 --> 00:50:37.180 But maybe lung cancer NOTE Confidence: 0.98086786 00:50:37.485 --> 00:50:39.485 presents with enough categories that NOTE Confidence: 0.98086786 00:50:39.485 --> 00:50:40.365 you can do a master NOTE Confidence: 0.98086786 00:50:40.365 --> 00:50:41.725 protocol where you give the NOTE Confidence: 0.98086786 00:50:41.725 --> 00:50:42.525 right drug to the right NOTE Confidence: 0.98086786 00:50:42.525 --> 00:50:44.205 person right up front. So NOTE Confidence: 0.98086786 00:50:44.205 --> 00:50:45.245 I would love to hear NOTE Confidence: 0.98086786 00:50:45.245 --> 00:50:46.685 if if that's what's made NOTE Confidence: 0.98086786 00:50:46.685 --> 00:50:47.885 them kind of this broader NOTE Confidence: 0.98086786 00:50:47.885 --> 00:50:49.405 approach successful in lung cancer, NOTE Confidence: 0.98086786 00:50:49.405 --> 00:50:49.905 Roy. NOTE Confidence: 0.9970127 00:50:50.319 --> 00:50:51.359 Well, of course, NOTE Confidence: 0.9075657 00:50:52.480 --> 00:50:54.160 lung cancer's evolved now with NOTE Confidence: 0.9075657 00:50:54.160 --> 00:50:55.940 nine different, you know, genetic, NOTE Confidence: 0.9513161 00:50:57.440 --> 00:50:59.599 defects, you know, oncogenes that NOTE Confidence: 0.9513161 00:50:59.599 --> 00:51:00.640 we can target that are NOTE Confidence: 0.9513161 00:51:00.640 --> 00:51:01.140 addicted, NOTE Confidence: 0.98221415 00:51:01.680 --> 00:51:03.119 that are addictive. So that NOTE Confidence: 0.98221415 00:51:03.119 --> 00:51:04.400 that opens up the door NOTE Confidence: 0.98221415 00:51:04.400 --> 00:51:05.415 there. I think the area NOTE Confidence: 0.98221415 00:51:05.415 --> 00:51:06.775 where these master protocols could NOTE Confidence: 0.98221415 00:51:06.775 --> 00:51:07.575 come in handy is in NOTE Confidence: 0.98221415 00:51:07.575 --> 00:51:09.435 resistance, either primary or acquired. NOTE Confidence: 0.99814403 00:51:09.735 --> 00:51:10.455 But you're right. You need NOTE Confidence: 0.99814403 00:51:10.455 --> 00:51:11.415 to have a dichotomy. You NOTE Confidence: 0.99814403 00:51:11.415 --> 00:51:12.614 can't solve the whole problem NOTE Confidence: 0.99814403 00:51:12.614 --> 00:51:13.355 at once. NOTE Confidence: 0.98870707 00:51:13.735 --> 00:51:14.535 You would need to find NOTE Confidence: 0.98870707 00:51:14.535 --> 00:51:15.655 patients who are resistant to NOTE Confidence: 0.98870707 00:51:15.655 --> 00:51:16.775 one therapy. And and then, NOTE Confidence: 0.98870707 00:51:16.775 --> 00:51:17.655 of course, there probably are NOTE Confidence: 0.98870707 00:51:17.655 --> 00:51:18.695 patients who are probably better NOTE Confidence: 0.98870707 00:51:18.695 --> 00:51:19.575 off with one drug than NOTE Confidence: 0.98870707 00:51:19.575 --> 00:51:20.559 the other, and that that NOTE Confidence: 0.98870707 00:51:20.559 --> 00:51:22.400 is precision medicine. And, we NOTE Confidence: 0.98870707 00:51:22.400 --> 00:51:23.440 certainly have the ability to NOTE Confidence: 0.98870707 00:51:23.440 --> 00:51:24.719 do that here. Right? One NOTE Confidence: 0.98870707 00:51:24.719 --> 00:51:25.440 of the things you'll work NOTE Confidence: 0.98870707 00:51:25.440 --> 00:51:26.480 on, William, because we have NOTE Confidence: 0.98870707 00:51:26.480 --> 00:51:28.400 the pathology is is amazing. NOTE Confidence: 0.98870707 00:51:28.400 --> 00:51:29.380 We have the surgical NOTE Confidence: 0.9635447 00:51:29.680 --> 00:51:30.799 colleagues who will co work NOTE Confidence: 0.9635447 00:51:30.799 --> 00:51:32.319 with us, radiation oncology. And NOTE Confidence: 0.9635447 00:51:32.319 --> 00:51:33.760 then in a multimodality way, NOTE Confidence: 0.9635447 00:51:33.760 --> 00:51:34.559 sort of pull that all NOTE Confidence: 0.9635447 00:51:34.559 --> 00:51:35.725 together. So I think that's NOTE Confidence: 0.9635447 00:51:35.725 --> 00:51:36.925 a good point, Joe. I NOTE Confidence: 0.9635447 00:51:36.925 --> 00:51:38.125 wanna ask you another question, NOTE Confidence: 0.9635447 00:51:38.125 --> 00:51:38.625 William, NOTE Confidence: 0.93822944 00:51:38.925 --> 00:51:40.605 and, other questions, Joe, who NOTE Confidence: 0.93822944 00:51:40.605 --> 00:51:42.204 has the other microphone. You're NOTE Confidence: 0.93822944 00:51:42.204 --> 00:51:43.484 at Greenwich, and you're setting NOTE Confidence: 0.93822944 00:51:43.484 --> 00:51:44.785 up a service line there. NOTE Confidence: 0.9373219 00:51:45.165 --> 00:51:45.984 The PMSA, NOTE Confidence: 0.9518317 00:51:46.525 --> 00:51:47.645 therapy you mentioned, is that NOTE Confidence: 0.9518317 00:51:47.645 --> 00:51:48.545 available there? NOTE Confidence: 0.9746192 00:51:49.244 --> 00:51:50.445 Is it available throughout our NOTE Confidence: 0.9746192 00:51:50.445 --> 00:51:52.180 network? And, then also the NOTE Confidence: 0.9746192 00:51:52.180 --> 00:51:53.140 BiTE therapy. I just came NOTE Confidence: 0.9746192 00:51:53.140 --> 00:51:54.100 off a couple weeks on NOTE Confidence: 0.9746192 00:51:54.100 --> 00:51:55.300 service, and I can tell NOTE Confidence: 0.9746192 00:51:55.300 --> 00:51:56.260 you that that's not the NOTE Confidence: 0.9746192 00:51:56.260 --> 00:51:57.460 easiest thing. Are we administering NOTE Confidence: 0.9746192 00:51:57.460 --> 00:51:58.340 that at all our centers NOTE Confidence: 0.9746192 00:51:58.340 --> 00:51:59.860 as well? Yeah. Well, the NOTE Confidence: 0.9746192 00:51:59.860 --> 00:52:01.460 imaging is available there in NOTE Confidence: 0.9746192 00:52:01.460 --> 00:52:03.480 Greenwich, and I'm meeting with NOTE Confidence: 0.9746192 00:52:03.620 --> 00:52:05.400 the nuclear medicine team tomorrow, NOTE Confidence: 0.9858577 00:52:06.245 --> 00:52:07.605 I believe, to talk about NOTE Confidence: 0.9858577 00:52:07.605 --> 00:52:08.405 how to make, NOTE Confidence: 0.99747217 00:52:08.725 --> 00:52:10.025 some of these treatments available, NOTE Confidence: 0.9879708 00:52:10.405 --> 00:52:12.005 in places like Greenwich. But NOTE Confidence: 0.9879708 00:52:12.005 --> 00:52:13.125 it is complicated. I think NOTE Confidence: 0.9879708 00:52:13.125 --> 00:52:14.505 you need the right expertise NOTE Confidence: 0.9879708 00:52:14.725 --> 00:52:15.844 in each site to be NOTE Confidence: 0.9879708 00:52:15.844 --> 00:52:17.145 able to deliver it safely NOTE Confidence: 0.9879708 00:52:17.285 --> 00:52:18.025 and effectively. NOTE Confidence: 0.9814072 00:52:18.480 --> 00:52:19.680 And I have no doubt NOTE Confidence: 0.9814072 00:52:19.680 --> 00:52:20.960 that over time, we'll build NOTE Confidence: 0.9814072 00:52:20.960 --> 00:52:22.080 that. I mean, one of NOTE Confidence: 0.9814072 00:52:22.080 --> 00:52:22.880 the reasons, as you know, NOTE Confidence: 0.9814072 00:52:22.880 --> 00:52:24.100 that I came to Greenwich NOTE Confidence: 0.9814072 00:52:24.400 --> 00:52:25.680 is that I I saw NOTE Confidence: 0.9814072 00:52:25.680 --> 00:52:27.300 its proximity to New York NOTE Confidence: 0.9814072 00:52:27.520 --> 00:52:28.719 and our ability to kind NOTE Confidence: 0.9814072 00:52:28.719 --> 00:52:30.400 of apply the great science NOTE Confidence: 0.9814072 00:52:30.400 --> 00:52:31.600 and the great clinical care NOTE Confidence: 0.9814072 00:52:31.600 --> 00:52:32.800 we deliver across the whole NOTE Confidence: 0.9814072 00:52:32.800 --> 00:52:34.265 Milo network, but in a NOTE Confidence: 0.9814072 00:52:34.265 --> 00:52:35.545 place where there's a high NOTE Confidence: 0.9814072 00:52:35.545 --> 00:52:36.985 concentration of people, which is NOTE Confidence: 0.9814072 00:52:36.985 --> 00:52:37.965 in the New York area. NOTE Confidence: 0.9814072 00:52:38.185 --> 00:52:39.305 I was in Manhattan for NOTE Confidence: 0.9814072 00:52:39.305 --> 00:52:40.265 a long time. People would NOTE Confidence: 0.9814072 00:52:40.344 --> 00:52:41.225 when I moved to Manhattan, NOTE Confidence: 0.9814072 00:52:41.225 --> 00:52:42.105 people were like, why does NOTE Confidence: 0.9814072 00:52:42.105 --> 00:52:43.705 Manhattan need another cancer center? NOTE Confidence: 0.9814072 00:52:43.705 --> 00:52:44.745 And it turned out Manhattan NOTE Confidence: 0.9814072 00:52:44.745 --> 00:52:46.530 needed another cancer center quite NOTE Confidence: 0.9814072 00:52:46.530 --> 00:52:47.810 significantly. There were patients who NOTE Confidence: 0.9814072 00:52:47.810 --> 00:52:49.489 were really not cared for NOTE Confidence: 0.9814072 00:52:49.489 --> 00:52:50.290 by some of the well NOTE Confidence: 0.9814072 00:52:50.290 --> 00:52:51.810 known institutions in New York NOTE Confidence: 0.9814072 00:52:51.810 --> 00:52:53.489 City because they didn't have NOTE Confidence: 0.9814072 00:52:53.489 --> 00:52:55.570 access, because, there's, it was NOTE Confidence: 0.9814072 00:52:55.570 --> 00:52:57.350 such a highly concentrated area. NOTE Confidence: 0.9814072 00:52:57.570 --> 00:52:59.570 So I think Greenwich represents NOTE Confidence: 0.9814072 00:52:59.570 --> 00:53:01.190 a real opportunity for us NOTE Confidence: 0.9814072 00:53:01.325 --> 00:53:02.785 to to to do research, NOTE Confidence: 0.9814072 00:53:02.845 --> 00:53:04.205 to do clinical care that's NOTE Confidence: 0.9814072 00:53:04.205 --> 00:53:05.425 at the highest level, NOTE Confidence: 0.9337543 00:53:05.805 --> 00:53:07.485 but we'll start with the NOTE Confidence: 0.9337543 00:53:07.485 --> 00:53:08.605 areas of treatment that we NOTE Confidence: 0.9337543 00:53:08.605 --> 00:53:10.065 know are safe and effective. NOTE Confidence: 0.965962 00:53:10.445 --> 00:53:11.325 And and in the long NOTE Confidence: 0.965962 00:53:11.325 --> 00:53:12.365 run, I think we want NOTE Confidence: 0.965962 00:53:12.365 --> 00:53:14.045 patients in Greenwich or in NOTE Confidence: 0.965962 00:53:14.045 --> 00:53:15.485 Westerly or anywhere within the NOTE Confidence: 0.965962 00:53:15.485 --> 00:53:16.750 Smilo network to get the NOTE Confidence: 0.965962 00:53:16.750 --> 00:53:18.590 best standards of care. Great. NOTE Confidence: 0.965962 00:53:18.590 --> 00:53:19.570 Any other questions? NOTE Confidence: 0.98905754 00:53:20.430 --> 00:53:21.070 Do we have any of NOTE Confidence: 0.98905754 00:53:21.070 --> 00:53:22.050 our fellows here? NOTE Confidence: 0.98311526 00:53:23.470 --> 00:53:24.750 I didn't think so. I'm NOTE Confidence: 0.98311526 00:53:24.750 --> 00:53:26.030 gonna sign an executive order NOTE Confidence: 0.98311526 00:53:26.030 --> 00:53:27.010 to get the fellows. NOTE Confidence: 0.8700145 00:53:27.470 --> 00:53:28.830 And and and, seriously, we NOTE Confidence: 0.8700145 00:53:28.830 --> 00:53:29.710 should have our fellows here. NOTE Confidence: 0.8700145 00:53:29.710 --> 00:53:30.830 This was a wonderful talk, NOTE Confidence: 0.8700145 00:53:30.830 --> 00:53:31.230 and, NOTE Confidence: 0.998158 00:53:31.635 --> 00:53:33.015 if anyone's listening online, NOTE Confidence: 0.9661856 00:53:33.395 --> 00:53:34.515 we're gonna we're gonna exchange NOTE Confidence: 0.9661856 00:53:34.515 --> 00:53:35.475 that. But but, William, let NOTE Confidence: 0.9661856 00:53:35.475 --> 00:53:36.355 me ask you. The precision NOTE Confidence: 0.9661856 00:53:36.355 --> 00:53:38.035 medicine tumor board, which we NOTE Confidence: 0.9661856 00:53:38.035 --> 00:53:39.155 started a while back and NOTE Confidence: 0.9661856 00:53:39.155 --> 00:53:40.535 then COVID sort of derailed. NOTE Confidence: 0.9661856 00:53:40.594 --> 00:53:41.555 But I would think that's NOTE Confidence: 0.9661856 00:53:41.555 --> 00:53:42.915 critical for a cancer center NOTE Confidence: 0.9661856 00:53:42.915 --> 00:53:44.375 that we get our scientists NOTE Confidence: 0.9661856 00:53:44.630 --> 00:53:45.430 and we get the people NOTE Confidence: 0.9661856 00:53:45.430 --> 00:53:46.550 that know how to analyze NOTE Confidence: 0.9661856 00:53:46.550 --> 00:53:47.930 the DNA and the epigenetics NOTE Confidence: 0.9666879 00:53:48.390 --> 00:53:49.270 and and pull that all NOTE Confidence: 0.9666879 00:53:49.270 --> 00:53:49.770 together. NOTE Confidence: 0.97468394 00:53:50.310 --> 00:53:51.590 You're gonna revitalize that, I NOTE Confidence: 0.97468394 00:53:51.590 --> 00:53:52.230 know. Can you tell us NOTE Confidence: 0.97468394 00:53:52.230 --> 00:53:53.830 your plans? Well, I think, NOTE Confidence: 0.97468394 00:53:53.830 --> 00:53:55.110 first of all, Zenta and NOTE Confidence: 0.97468394 00:53:55.110 --> 00:53:56.469 Rick Wilson Zenta Walter and NOTE Confidence: 0.97468394 00:53:56.469 --> 00:53:57.510 Rick Wilson have done a NOTE Confidence: 0.97468394 00:53:57.510 --> 00:53:58.710 really great job of taking NOTE Confidence: 0.97468394 00:53:58.710 --> 00:54:00.174 this over from Qualator. But NOTE Confidence: 0.97468394 00:54:00.174 --> 00:54:01.234 I do think that, NOTE Confidence: 0.9446833 00:54:02.255 --> 00:54:03.295 the goal is to kind NOTE Confidence: 0.9446833 00:54:03.295 --> 00:54:03.795 of NOTE Confidence: 0.9812243 00:54:04.094 --> 00:54:05.795 not just teach, but really NOTE Confidence: 0.9812243 00:54:05.855 --> 00:54:07.214 affect the care of all NOTE Confidence: 0.9812243 00:54:07.214 --> 00:54:08.255 the patients who get this NOTE Confidence: 0.9812243 00:54:08.255 --> 00:54:10.255 molecular testing across all the NOTE Confidence: 0.9812243 00:54:10.255 --> 00:54:11.614 diseases that we see. We NOTE Confidence: 0.9812243 00:54:11.614 --> 00:54:12.734 have an amazing phase one NOTE Confidence: 0.9812243 00:54:12.734 --> 00:54:14.255 program. And in a way, NOTE Confidence: 0.9812243 00:54:14.255 --> 00:54:15.870 a precision medicine tumor board NOTE Confidence: 0.9812243 00:54:15.950 --> 00:54:16.850 is like matchmaking. NOTE Confidence: 0.98855746 00:54:17.150 --> 00:54:18.670 It's like finding the genetic NOTE Confidence: 0.98855746 00:54:18.670 --> 00:54:20.430 results that would lead patients NOTE Confidence: 0.98855746 00:54:20.430 --> 00:54:21.870 to go on trials sooner NOTE Confidence: 0.98855746 00:54:21.870 --> 00:54:23.150 and faster. We know the NOTE Confidence: 0.98855746 00:54:23.150 --> 00:54:24.910 biggest barrier. I showed that NOTE Confidence: 0.98855746 00:54:24.910 --> 00:54:26.530 biomarker slide from the FDA. NOTE Confidence: 0.98855746 00:54:26.750 --> 00:54:28.350 The biggest barrier that that NOTE Confidence: 0.98855746 00:54:28.350 --> 00:54:29.890 industry has with these drugs NOTE Confidence: 0.98855746 00:54:29.950 --> 00:54:31.070 is finding patients to go NOTE Confidence: 0.98855746 00:54:31.070 --> 00:54:32.525 on their trials. And cancer NOTE Confidence: 0.98855746 00:54:32.525 --> 00:54:34.205 is no longer prostate cancer, NOTE Confidence: 0.98855746 00:54:34.205 --> 00:54:35.725 lung cancer, breast cancer. It NOTE Confidence: 0.98855746 00:54:35.725 --> 00:54:36.225 is, NOTE Confidence: 0.9635251 00:54:37.325 --> 00:54:39.245 increasingly rare diseases because they're NOTE Confidence: 0.9635251 00:54:39.245 --> 00:54:41.185 subsetted into these molecular subtypes. NOTE Confidence: 0.9443885 00:54:41.485 --> 00:54:42.765 So I think a precision NOTE Confidence: 0.9443885 00:54:42.765 --> 00:54:43.965 medicine tumor board is really NOTE Confidence: 0.9443885 00:54:43.965 --> 00:54:45.405 critical, and, my goal is NOTE Confidence: 0.9443885 00:54:45.405 --> 00:54:46.680 to think about ways that NOTE Confidence: 0.9443885 00:54:46.680 --> 00:54:47.800 we can improve it, make NOTE Confidence: 0.9443885 00:54:47.800 --> 00:54:48.460 it hybrid, NOTE Confidence: 0.95223397 00:54:48.760 --> 00:54:50.280 and think about more frequent NOTE Confidence: 0.95223397 00:54:50.280 --> 00:54:51.739 and and really tactical NOTE Confidence: 0.9327213 00:54:52.200 --> 00:54:53.960 discussion so that both trainees NOTE Confidence: 0.9327213 00:54:53.960 --> 00:54:55.319 and and the docs themselves NOTE Confidence: 0.9327213 00:54:55.319 --> 00:54:56.520 really learn from the experience, NOTE Confidence: 0.9327213 00:54:56.520 --> 00:54:58.200 including myself. Great. Speaking of NOTE Confidence: 0.9327213 00:54:58.200 --> 00:54:59.000 multiple data, we have a NOTE Confidence: 0.9327213 00:54:59.000 --> 00:55:00.619 chair of urology, doctor Kim. NOTE Confidence: 0.9327213 00:55:00.815 --> 00:55:02.015 Well, again, thank you so NOTE Confidence: 0.9327213 00:55:02.015 --> 00:55:03.295 much for the talk. I NOTE Confidence: 0.9327213 00:55:03.295 --> 00:55:04.335 just wanna go back to NOTE Confidence: 0.9327213 00:55:04.335 --> 00:55:05.855 the, the disparity issue with NOTE Confidence: 0.9327213 00:55:05.855 --> 00:55:07.375 the black man. So, again, NOTE Confidence: 0.9327213 00:55:07.375 --> 00:55:08.015 I think we as a NOTE Confidence: 0.9327213 00:55:08.015 --> 00:55:09.055 field have been talking about NOTE Confidence: 0.9327213 00:55:09.055 --> 00:55:10.255 this for a long, long NOTE Confidence: 0.9327213 00:55:10.255 --> 00:55:10.755 time. NOTE Confidence: 0.9037219 00:55:11.055 --> 00:55:12.255 So the suggestions in the NOTE Confidence: 0.9037219 00:55:12.415 --> 00:55:13.329 I read the your papers. NOTE Confidence: 0.9037219 00:55:13.329 --> 00:55:14.369 How do you implement something NOTE Confidence: 0.9037219 00:55:14.369 --> 00:55:15.089 like that? What are your NOTE Confidence: 0.9037219 00:55:15.089 --> 00:55:16.450 thoughts on getting it out NOTE Confidence: 0.9037219 00:55:16.450 --> 00:55:17.489 into the community to make NOTE Confidence: 0.9037219 00:55:17.489 --> 00:55:19.250 sure that such guidelines are NOTE Confidence: 0.9037219 00:55:19.250 --> 00:55:20.290 followed? Because there's still some NOTE Confidence: 0.9037219 00:55:20.290 --> 00:55:21.190 huge resistance, NOTE Confidence: 0.95132655 00:55:21.809 --> 00:55:22.930 in terms of implementing. So NOTE Confidence: 0.95132655 00:55:22.930 --> 00:55:23.809 what challenge do you see NOTE Confidence: 0.95132655 00:55:23.809 --> 00:55:25.569 and, your thoughts? I I NOTE Confidence: 0.95132655 00:55:25.650 --> 00:55:26.950 yeah. It's a great question, NOTE Confidence: 0.95132655 00:55:27.010 --> 00:55:27.809 Isaac, because, NOTE Confidence: 0.96317554 00:55:28.645 --> 00:55:29.605 sometimes the people who are NOTE Confidence: 0.96317554 00:55:29.605 --> 00:55:31.285 the biggest evangelists for finding NOTE Confidence: 0.96317554 00:55:31.285 --> 00:55:32.905 these cancers earlier, like urologists NOTE Confidence: 0.96317554 00:55:32.965 --> 00:55:34.325 or oncologists, are not the NOTE Confidence: 0.96317554 00:55:34.325 --> 00:55:35.625 ones talking to the patients NOTE Confidence: 0.96317554 00:55:35.765 --> 00:55:37.525 in primary care. I think NOTE Confidence: 0.96317554 00:55:37.525 --> 00:55:38.565 that there's a way to NOTE Confidence: 0.96317554 00:55:38.565 --> 00:55:40.565 implement a smile wide, Yale NOTE Confidence: 0.96317554 00:55:40.565 --> 00:55:41.065 wide, NOTE Confidence: 0.9880726 00:55:41.559 --> 00:55:42.520 program. This is really not NOTE Confidence: 0.9880726 00:55:42.520 --> 00:55:43.900 a cancer issue. It's precancerous. NOTE Confidence: 0.9880726 00:55:43.960 --> 00:55:45.719 It's really internal medicine where NOTE Confidence: 0.9880726 00:55:45.719 --> 00:55:46.219 we NOTE Confidence: 0.95955765 00:55:46.839 --> 00:55:48.359 try to convey this idea NOTE Confidence: 0.95955765 00:55:48.359 --> 00:55:49.960 and and to create, maybe NOTE Confidence: 0.95955765 00:55:49.960 --> 00:55:51.180 a Yale wide program NOTE Confidence: 0.9692069 00:55:51.559 --> 00:55:52.520 for looking at these high NOTE Confidence: 0.9692069 00:55:52.520 --> 00:55:54.280 risk populations. That includes black NOTE Confidence: 0.9692069 00:55:54.280 --> 00:55:55.099 men. It includes NOTE Confidence: 0.98354423 00:55:55.400 --> 00:55:57.099 men with, genetic risk. NOTE Confidence: 0.9607823 00:55:57.855 --> 00:55:58.735 And I think this publication NOTE Confidence: 0.9607823 00:55:58.735 --> 00:55:59.695 of this guideline, the reason NOTE Confidence: 0.9607823 00:55:59.695 --> 00:56:00.515 I think NEJM, NOTE Confidence: 0.93592906 00:56:01.375 --> 00:56:03.135 evidence allowed us to publish NOTE Confidence: 0.93592906 00:56:03.135 --> 00:56:04.435 it was they recognize NOTE Confidence: 0.999643 00:56:04.735 --> 00:56:05.875 this gap between NOTE Confidence: 0.9803539 00:56:06.175 --> 00:56:07.715 this idea that the USPSTF NOTE Confidence: 0.9803539 00:56:07.935 --> 00:56:09.555 says there's not enough evidence, NOTE Confidence: 0.9803539 00:56:09.614 --> 00:56:11.530 and now we have something NOTE Confidence: 0.9803539 00:56:11.530 --> 00:56:13.049 that can justify a program NOTE Confidence: 0.9803539 00:56:13.049 --> 00:56:14.170 where we're more aggressive about NOTE Confidence: 0.9803539 00:56:14.170 --> 00:56:15.849 screening black men. So I NOTE Confidence: 0.9803539 00:56:15.849 --> 00:56:17.049 wanna certainly sit down with NOTE Confidence: 0.9803539 00:56:17.049 --> 00:56:19.049 you and your department, but NOTE Confidence: 0.9803539 00:56:19.049 --> 00:56:21.309 also internal medicine, primary care, NOTE Confidence: 0.9506348 00:56:21.609 --> 00:56:23.450 and, you know, AAFP and, NOTE Confidence: 0.9506348 00:56:23.530 --> 00:56:24.974 you know, ACP, NOTE Confidence: 0.9586474 00:56:25.275 --> 00:56:26.555 the American College of Physicians, NOTE Confidence: 0.9586474 00:56:26.555 --> 00:56:27.594 they're kind of still against NOTE Confidence: 0.9586474 00:56:27.594 --> 00:56:28.094 screening. NOTE Confidence: 0.98543817 00:56:28.555 --> 00:56:29.855 And this is the problem. NOTE Confidence: 0.98543817 00:56:29.994 --> 00:56:31.515 Risk adapted screening is the NOTE Confidence: 0.98543817 00:56:31.515 --> 00:56:32.954 key. Don't screen everyone. Don't NOTE Confidence: 0.98543817 00:56:32.954 --> 00:56:34.494 screen the ninety year old NOTE Confidence: 0.98543817 00:56:34.555 --> 00:56:35.435 guy who comes in a NOTE Confidence: 0.98543817 00:56:35.435 --> 00:56:37.194 wheelchair. But a fifty year NOTE Confidence: 0.98543817 00:56:37.194 --> 00:56:38.234 old or forty five year NOTE Confidence: 0.98543817 00:56:38.234 --> 00:56:39.670 old black man who has NOTE Confidence: 0.98543817 00:56:39.670 --> 00:56:41.190 a family history, he's getting NOTE Confidence: 0.98543817 00:56:41.190 --> 00:56:42.550 the wrong message. I know NOTE Confidence: 0.98543817 00:56:42.550 --> 00:56:44.150 that because they're they're not NOTE Confidence: 0.98543817 00:56:44.150 --> 00:56:45.510 being told that they should NOTE Confidence: 0.98543817 00:56:45.510 --> 00:56:46.790 be detected trying to detect NOTE Confidence: 0.98543817 00:56:46.790 --> 00:56:48.469 this cancer. So I think NOTE Confidence: 0.98543817 00:56:48.469 --> 00:56:49.430 it is a huge challenge. NOTE Confidence: 0.98543817 00:56:49.430 --> 00:56:50.710 I think ACS is very NOTE Confidence: 0.98543817 00:56:50.710 --> 00:56:52.710 interested in creating the the NOTE Confidence: 0.98543817 00:56:52.710 --> 00:56:53.670 the the toolkit to be NOTE Confidence: 0.98543817 00:56:53.670 --> 00:56:55.094 able to help places do NOTE Confidence: 0.98543817 00:56:55.094 --> 00:56:56.215 this, and that's, I think, NOTE Confidence: 0.98543817 00:56:56.215 --> 00:56:56.955 another source NOTE Confidence: 0.9994265 00:56:57.415 --> 00:56:57.995 of information. NOTE Confidence: 0.9942248 00:56:59.255 --> 00:57:00.455 Any other questions? I think NOTE Confidence: 0.9942248 00:57:00.455 --> 00:57:01.015 we are at the end NOTE Confidence: 0.9942248 00:57:01.015 --> 00:57:01.815 of the hour. I'll just NOTE Confidence: 0.9942248 00:57:01.815 --> 00:57:02.535 say that this is a NOTE Confidence: 0.9942248 00:57:02.535 --> 00:57:04.055 wonderful example of what, NOTE Confidence: 0.97141784 00:57:04.375 --> 00:57:05.975 comprehensive cancer center does. You NOTE Confidence: 0.97141784 00:57:05.975 --> 00:57:07.170 know, we go from the NOTE Confidence: 0.97141784 00:57:07.170 --> 00:57:07.670 patient, NOTE Confidence: 0.97252446 00:57:08.210 --> 00:57:09.730 access, you know, bringing people NOTE Confidence: 0.97252446 00:57:09.730 --> 00:57:11.170 in and getting them screened, NOTE Confidence: 0.97252446 00:57:11.170 --> 00:57:12.050 taking them all the way NOTE Confidence: 0.97252446 00:57:12.050 --> 00:57:13.109 through the new therapeutic NOTE Confidence: 0.77021724 00:57:13.969 --> 00:57:14.469 options. NOTE Confidence: 0.99259454 00:57:14.770 --> 00:57:16.869 We have wonderful surgery, radiation, NOTE Confidence: 0.89890414 00:57:17.250 --> 00:57:18.050 a a large number of NOTE Confidence: 0.89890414 00:57:18.050 --> 00:57:20.210 medical oncologists, Dan, yourself, Joe NOTE Confidence: 0.89890414 00:57:20.210 --> 00:57:21.109 Kim is here, NOTE Confidence: 0.92510617 00:57:21.675 --> 00:57:22.975 many others. We have Sameer NOTE Confidence: 0.92510617 00:57:23.035 --> 00:57:24.175 Azadi coming from, NOTE Confidence: 0.9619583 00:57:25.035 --> 00:57:26.075 New York who works on NOTE Confidence: 0.9619583 00:57:26.075 --> 00:57:27.355 plasticity, right, who works on NOTE Confidence: 0.9619583 00:57:27.355 --> 00:57:28.635 the developmental. So we have NOTE Confidence: 0.9619583 00:57:28.635 --> 00:57:29.355 so much that we can NOTE Confidence: 0.9619583 00:57:29.355 --> 00:57:30.801 do here. So, let you NOTE Confidence: 0.9619583 00:57:30.801 --> 00:57:31.841 know, you should start thinking NOTE Confidence: 0.9619583 00:57:31.841 --> 00:57:32.801 about, like, a spore in NOTE Confidence: 0.9619583 00:57:32.801 --> 00:57:33.781 a few years. So, NOTE Confidence: 0.9726896 00:57:34.081 --> 00:57:35.201 really great to see everyone NOTE Confidence: 0.9726896 00:57:35.201 --> 00:57:36.561 here. William will stay up NOTE Confidence: 0.9726896 00:57:36.561 --> 00:57:37.521 for a few more questions, NOTE Confidence: 0.9726896 00:57:37.521 --> 00:57:37.841 and, NOTE Confidence: 0.9982244 00:57:38.321 --> 00:57:39.121 enjoy the rest of your NOTE Confidence: 0.9982244 00:57:39.121 --> 00:57:39.906 day. Thank you.