Tumor Type Series: SCLCa

Transcript

• 00:07So I'm going to just start out by
• 00:09saying give you a little background
• 00:11on small cell before we get to sort
• 00:14of the the the life cycle that Natural
• 00:17History and and how we treat it.
• 00:19So there are basically two
• 00:21types of lung cancer.
• 00:22There's small cell lung cancer
• 00:24which is about 13 to 15%.
• 00:26Everything else is non
• 00:28small cell lung cancer.
• 00:30You know, as you know and you'll find
• 00:32out non small cell they're different.
• 00:36Flavors, soap taste, vanilla chocolate,
• 00:40pistachio that's squamous,
• 00:42adeno cursing, and so forth.
• 00:43And then you break those down
• 00:45in terms of molecular subtypes,
• 00:47but I'm concentrating on small cell.
• 00:50Today and. Small cell is called back oops.
• 00:57Let me skip to this one because of what
• 00:59it looks like underneath the microscope,
• 01:01so these are these small blue cells.
• 01:04And it's characterized by very
• 01:08rapid proliferation time.
• 01:10You know,
• 01:11it metastasizes early development
• 01:12of Mets to other places.
• 01:15And because it's growing so quickly,
• 01:17it also is very sensitive to
• 01:21both chemotherapy and radiation.
• 01:23So for pathology,
• 01:24these are small blue style cells.
• 01:27There's very sparse cytoplasm.
• 01:29You often see nuclear molding or
• 01:32what they call also crush artifact.
• 01:35It's a high grade neuroendocrine tumor,
• 01:37which means that there are.
• 01:42Markers positive for for some
• 01:44of these neuroendocrine cells.
• 01:46Chromogranin snap to fizan.
• 01:48Those are some of the things that we look at.
• 01:52So small cell, I'll just go back to that
• 01:55other slide that just sort of says.
• 01:58We have some problems there we go.
• 02:00This was a paper from the New England
• 02:03Journal of Medicine two years ago that
• 02:05actually showed that there's a decrease
• 02:08in both the incidence and mortality
• 02:10of small cell amongst men and women.
• 02:12So that's that.
• 02:13We saw that in non small cell
• 02:15also in small stone that properly
• 02:17reflects the decreases in smoking.
• 02:24It terms of staging.
• 02:25This is how we do the staging on the
• 02:28left here and this is from the via
• 02:30VA study that came that was really
• 02:33done at back in the 70s and what we
• 02:35say is that that you are basically
• 02:38limited stage versus extensive stage
• 02:40and extensive stage is the same thing.
• 02:43If you have a metastasis to different
• 02:46parts of your body and or different
• 02:49organs or in the pleural fluid.
• 02:52And limited means that you're really
• 02:55just limited to the thorax and,
• 02:57and that's important because limited
• 02:59allows you to or actually thorax,
• 03:02and specifically a radiation portal.
• 03:04For limited disease we we
• 03:06consider radiation plus chemo.
• 03:08Extensive is just systemic therapy and
• 03:11and that's a little bit different from the
• 03:15TNM staging that we use in in non small cell.
• 03:18We still collect this information
• 03:21on tumor nodes and metastases.
• 03:23It's important for our trials,
• 03:25but it it doesn't guide the treatment
• 03:27in the same way as non small cell.
• 03:30But we still collect that because
• 03:32it's really important for prognosis.
• 03:35So if you look at limited stage disease,
• 03:38those patients who are again so you know
• 03:41you could imagine a radiation portal,
• 03:43including a tumor that's in
• 03:45one part of the lung.
• 03:46Maybe some of the lymph nodes involved
• 03:49sometimes are radox are really good.
• 03:51They can get to some lymph
• 03:52nodes on the other side,
• 03:53but if you had fluid.
• 03:57You're not going to be able to
• 04:01definitively radiate fluid or.
• 04:03You know involvement in other organs or
• 04:06lots of disease on on both sides just can't.
• 04:09Just too much of that radiation
• 04:11field is too much,
• 04:12so if you're limited and you can
• 04:15treat by sterilization with with them.
• 04:18Radiation and concurrent chemotherapy.
• 04:21Then the median survival, and these.
• 04:23These are changing a little bit.
• 04:25This is more historical.
• 04:27Is is 16 to 20 you know 16 to 24 months.
• 04:33There are some people.
• 04:35This is the aim here for limited stage
• 04:38is still curative so you do have some
• 04:41patients who are are out five years.
• 04:44You know this is somewhere around 15 to
• 04:4725% of those patients are still alive.
• 04:50As opposed to metastatic or
• 04:52extensive stage disease,
• 04:53I guess I should have said
• 04:55extensive here and this traditional.
• 04:57Historically,
• 04:58the median survival has been pretty
• 05:00dismal around 12 months and almost
• 05:04no no patients making it out to to
• 05:06two years and treated with systemic
• 05:09treatment that goes through your bloodstream.
• 05:12This is changing and I'll show you
• 05:14some of that data which is really exciting.
• 05:17So this is a review that.
• 05:21Matt did when he was a fellow here and
• 05:24and this is it just shows you that
• 05:27through the decades there really few
• 05:29and far between major milestones and
• 05:32small so they had to do with chemotherapy,
• 05:35cisplatin,
• 05:35etoposide,
• 05:36the regimen that we still use was
• 05:39developed in the 19 in 1990.
• 05:44At our 1986 and you know here
• 05:47the big milestone was using
• 05:50prophylactic cranial radiation or
• 05:53thoracic radiation consolidation.
• 05:55But now in the past two
• 05:59years there have been. 3.
• 06:043 regiments that are FDA
• 06:07have been FDA approved.
• 06:08Actually, they've been.
• 06:10Sort of more, but then some of
• 06:12them have been pulled back and I'll
• 06:14talk a little bit more about that,
• 06:15so I'm going to talk about first
• 06:17the two trials that have changed
• 06:19the how patients are treated in
• 06:21the frontline therapy in frontline
• 06:24therapy when they're diagnosed.
• 06:26But I thought what I'd start
• 06:27out is is with a patient case.
• 06:29So you sort of see how how this
• 06:32patient will present when,
• 06:33when when I meet them and and sort of
• 06:37their story. So this is my patient.
• 06:40It's an 83 year old African American woman.
• 06:43She had a 40 pack year tobacco
• 06:45history and she presented 2 years
• 06:48ago with weight loss, worsening,
• 06:50shortness of breath,
• 06:51abdominal discomfort and then
• 06:53on physical exam.
• 06:54She had lymph nodes in her neck and
• 06:57her right armpit and this is her
• 07:00pet scan and you can see this big
• 07:03very hyper metabolic active hyper.
• 07:06Very pet avid right? Lower low mass.
• 07:10Some other tumor nodules.
• 07:12There lots of lymph nodes that you
• 07:15can't see in this particular section.
• 07:17Her brain MRI was negative and a
• 07:19biopsy of her lymph node showed small
• 07:22cell that was positive for these markers.
• 07:25And this is Ki.
• 07:2667 is a marker of
• 07:29proliferation and that's 90%.
• 07:31That means 90% of the tumor cells in
• 07:34that underneath the scope and that.
• 07:37In that section are dividing,
• 07:39so that's why these are.
• 07:41They're really sensitive to chemotherapy
• 07:44because they're dividing so quickly.
• 07:48So how would you treat this patient?
• 07:50Well,
• 07:50if this patient is in the hospital,
• 07:53then we typically treat this
• 07:55patient with chemotherapy,
• 07:56and we specifically probably Carbo etoposide,
• 08:01potentially etoposide,
• 08:02and we would not add that that
• 08:06immunotherapy until their second cycle or
• 08:08or after they come out of the hospital.
• 08:13If I meet them, if I meet them in the office,
• 08:16both of these regiments, being C,
• 08:18have been BC&D actually have been approved.
• 08:22The fee is the Empower 133 trial
• 08:27CD's are the Caspian trial trial and
• 08:29I'll show that to you in a moment.
• 08:34So actually, all of these are correct.
• 08:37OK, so let's look at the Empower 133 trial.
• 08:40So for this trial,
• 08:42the patients who are newly diagnosed,
• 08:45they hadn't gotten any treatment yet
• 08:47and they were randomized to two arms.
• 08:50One is the standard of care carboplatinum,
• 08:53etoposide, plus placebo and then the
• 08:56other is chemo plus atezolizumab and
• 08:59then followed by maintenance ateso or
• 09:02placebo treating until progression
• 09:04of disease or loss of benefit.
• 09:07And so. This trial this is the
• 09:10Kaplan Meier curve and this is what
• 09:13we look at for over survival.
• 09:15The the blue is the arm with
• 09:19the immunotherapy atezolizumab.
• 09:20The red is the placebo and what we're
• 09:22looking for in this kind of curve
• 09:25is a difference between the arms
• 09:27that is statistically significant.
• 09:29Now if you look at there's two
• 09:30ways to look at these curves.
• 09:32OK, one is we look at the median
• 09:35overall survival for all the
• 09:37patients in the experimental.
• 09:39Arm versus placebo and you can see
• 09:41that those patients on average lived
• 09:44two months more than placebos.
• 09:46Even like, well, two months is that.
• 09:47I mean, yes,
• 09:49it's it's important and it's significant.
• 09:51But what we're really looking at with
• 09:54immunotherapy is whether we can really
• 09:56change what we call the tail of this curve.
• 09:58So as time goes out in months,
• 10:02will more and more of these patients exhibit.
• 10:06Benefit because we've sort of taught their
• 10:09immune system to recognize cancer cells
• 10:12and and and and and continue to destroy them.
• 10:15So that's why these this sort of
• 10:18what's called a landmark analysis.
• 10:21So at one mark,
• 10:22so landmark at 12 year at 12
• 10:25months or 18 months,
• 10:27you look at the difference.
• 10:28Here's 34 at 18 months,
• 10:3134% of the patients are alive
• 10:33versus 21 on the placebo and and.
• 10:35And I want you to.
• 10:36This is important because as we move out,
• 10:40you'll see for the Caspian trial we have
• 10:42three year data that's really promising.
• 10:45OK, so that's any questions on that so far.
• 10:49I know I'm throwing a lot of stuff to you,
• 10:50but you know this is stuff for you guys.
• 10:52Put patients on this trial on these trials
• 10:55so this is showing you the results of that.
• 10:57Any questions so far?
• 11:01I'm going to pick on somebody.
• 11:04Omar, any questions?
• 11:08No, not yet doctor change your.
• 11:10Is this making sense to you so far?
• 11:13Yes OK, OK thank you.
• 11:16Thank you for answering.
• 11:17OK so then this this is the
• 11:20next question here, you know?
• 11:22This patient had excellent response
• 11:24to four cycles of treatment and
• 11:27then she continues maintenance
• 11:29on monthly atezolizumab and
• 11:31the the teaser was tolerated.
• 11:33Well, except for she did have
• 11:36immunotherapy induced rash that was
• 11:38controlled with steroid topical cream.
• 11:40So she's now in cycle nine
• 11:42of monthly at Tiso.
• 11:43How long do we continue this?
• 11:47Had nice response. See remember that
• 11:49that right lower lobe down here.
• 11:51That's gotten a lot better and and so
• 11:54of course the the length of maintenance
• 11:57therapy has to do with how well the
• 12:01the treatment is tolerated, right?
• 12:03So that's why we ask and collect
• 12:06information around safety and adverse
• 12:08events and so this basically shows you
• 12:12the difference between the ateso arm,
• 12:14the experimental arm and then
• 12:16the placebo arm.
• 12:18Is basically exactly the same.
• 12:19This is kind of interesting
• 12:21to me because here you know,
• 12:23because you you don't know
• 12:25whether you're on drug or placebo.
• 12:27You can see in the placebo arm people
• 12:30are still reporting treatment related AE
• 12:32even though we know they're not getting.
• 12:36They're just getting placebo,
• 12:37but they're actually relating
• 12:39grade 3/4 events too.
• 12:41You know to their adverse events so
• 12:43that that I think is interesting,
• 12:46but on the whole,
• 12:47this is pretty pretty much
• 12:49well tolerated the the,
• 12:51the median duration of ateso
• 12:54treatment was 4.7 months.
• 12:57The median treatment duration of
• 13:00placebo was about the same and
• 13:03the cumulative doses of baptizo
• 13:05you got about 7 doses of it.
• 13:09So what what this says to me, is that OK?
• 13:11These arms are pretty well balanced,
• 13:13and it's pretty well, you know,
• 13:15there's not a major safety concern in
• 13:18in in adding the adhesiveness about.
• 13:21OK. So.
• 13:25This is another patient of mine,
• 13:27and in this case,
• 13:29and this is again how he presented all right.
• 13:32So he presented last spring 67 year old,
• 13:3650 pack year tobacco history with
• 13:39weight loss over several months.
• 13:41Difficulty eating.
• 13:42That's a dysphagia, or swallowing,
• 13:45worsening shortness of breath
• 13:46on exertion and weakness,
• 13:48and so the CAT scan that he had
• 13:51showed a very bulky mediastinal
• 13:53mask that was extending into the SVC
• 13:56in the right upper lobe bronchus,
• 13:58and he had bulky lymph nodes
• 14:01and multiple satellite nodules.
• 14:02Throughout the right lung and then
• 14:05you see here. OK the brain MRI.
• 14:08Numerous sub center meteor lesions
• 14:10and and this is very typical of our
• 14:13small cell patients that this that
• 14:15they will have spread to the brain.
• 14:18So he also underwent a biopsy.
• 14:21And do a bronchial ultrasound and
• 14:23biopsy of the right upper lung node
• 14:25will and the lymph nodes and that
• 14:27showed small cell lung cancer.
• 14:29So what's the next step in treatment?
• 14:32So in this case,
• 14:34I'll just mention this because it
• 14:36comes up if you don't have symptoms
• 14:38then we can start with the systemic therapy.
• 14:41If there are symptoms that are
• 14:43concerning so you know focal
• 14:45neurological symptoms or something like that,
• 14:48then we might invoke or we might
• 14:51utilize surgery or brain radiation
• 14:53before we get started on the
• 14:56systemic therapy.
• 14:57So this is it,
• 14:58you know important distinction
• 14:59whether or not you have symptoms,
• 15:00obviously,
• 15:01but but this is the the other frontline
• 15:04trial that led to the standard of care,
• 15:07and this is called the Caspian and
• 15:09they actually did allow patients with
• 15:12asymptomatic brain Mets to go on trial.
• 15:15The previous trial that I told you about
• 15:17only allowed patients with treated brain,
• 15:19Mets, and and as you know,
• 15:22many of you who worked on my trial,
• 15:24we do allow asymptomatic brain
• 15:26Mets and that's something that.
• 15:28We have to be very careful about to monitor,
• 15:31but on the other hand you know
• 15:33we do have good very good.
• 15:37Good effect with with systemic therapy.
• 15:41It's important to mention that because
• 15:44you know there is a blood brain
• 15:46barrier and there are other tumors
• 15:48that are less chemotherapy sensitive.
• 15:51But in this case small cell chemotherapy
• 15:53works pretty well even in the brain.
• 15:57So the Caspian study was again
• 16:00patients who had been never treated,
• 16:01just been diagnosed,
• 16:03and they had a good performance status,
• 16:06and they had asymptomatic.
• 16:09Brain Mets or treated brain. Mets.
• 16:12And they there's a hundred 800 patients.
• 16:15Some 805 patients randomized to three arms,
• 16:19so this is durva plus chemo durva
• 16:24Treme plus chemo or just chemo
• 16:27followed by maintenance and so.
• 16:31The Durva Treme arm actually did
• 16:34not show any significant difference
• 16:37between when compared to the.
• 16:40The chemo placebo.
• 16:41Sorry the chemo arm.
• 16:42I'm not going to talk about that but
• 16:45I am going to show you the data for
• 16:47the durva arm in the next slide.
• 16:49So again, the chain,
• 16:50can I ask a quick question
• 16:52that's in the chat?
• 16:53Yeah,
• 16:53so I think it's for the previous patient,
• 16:57but they said when you
• 16:59mentioned if the patient.
• 17:03You would give them chemo alone
• 17:05and possibly immunotherapy.
• 17:06Outpatient is that because
• 17:09of insurance coverage.
• 17:11You know the the that's exactly right,
• 17:15so the the immunotherapy,
• 17:18super expensive and it's something
• 17:20that we don't expect to to make
• 17:23a difference or very quickly,
• 17:25at least in in our hands.
• 17:26I mean that the key thing is the chemo.
• 17:28So typically what we'll do is
• 17:30we'll get that for cycle started
• 17:33in house and then start the Prius.
• 17:35They can get immunotherapy with the
• 17:37second cycle there is a there is.
• 17:40This is relatively new there is.
• 17:42They that both the companies the sponsors
• 17:46applied for what's called an end tap.
• 17:49That's an additional reimbursement
• 17:51payment for inpatient use,
• 17:53but we haven't really gotten to the
• 17:55point where we're we're utilizing that,
• 17:58and there's no data that shows that
• 18:00if you start with second cycle,
• 18:01it's any worse or better for that matter.
• 18:04So good question, really good question.
• 18:08OK, so this is the this is this
• 18:11Caspian study and this shows you
• 18:13the you know the the bottom line.
• 18:16This is an overall survival
• 18:19Kaplan Meier curve.
• 18:20And so what's really exciting about
• 18:22this and the first you know again,
• 18:25one metric is the median overall
• 18:28survival in the experimental arm,
• 18:3013 months versus 10 pretty
• 18:33much identical to the last one.
• 18:35What's really exciting is this
• 18:37was just presented.
• 18:38The updated analysis and at three years
• 18:41you can see how these curves are separating,
• 18:45so the blue or the patients who've
• 18:48been treated with chemo plus jurva.
• 18:51And at three years,
• 18:5318% of those are alive versus 6% when
• 18:59they were just treated with chemo.
• 19:00So this is pretty amazing.
• 19:02It's a tripling of the of the
• 19:05overall survival.
• 19:06I told you up front that historically
• 19:08most of the patients had like a less
• 19:11than two percent five year overall
• 19:14survival and and right now we're at 18%,
• 19:17so we're hoping that this this bears out now.
• 19:21Understandably,
• 19:21this means there are a lot of
• 19:23patients who have who have died
• 19:25who are not seeing this benefit,
• 19:27and so that's why we're so,
• 19:28you know,
• 19:29we're so active and in trying to
• 19:31do more research to understand.
• 19:35Understand who who can benefit
• 19:37and how to how to improve that.
• 19:39How to get more people to
• 19:41benefit from these therapies?
• 19:46Again, if you look at both arms,
• 19:49there's really very little
• 19:51difference in the serious ages,
• 19:53and there are, you know, pretty pretty.
• 19:55You know 5% or lower in in terms
• 19:58of the the the serious one, so.
• 20:04Oops, go back. So these are those two
• 20:06trials I just covered the Empower
• 20:09133 with a tizo Caspian with durva
• 20:13again the median overall survival
• 20:16very similar and the the Caspian.
• 20:20Showing that three year overall survival
• 20:23data, the difference in terms of the
• 20:26Caspian allowing asymptomatic brain,
• 20:28Mets and cisplatin and then the mention
• 20:31of those new technology add-on payments.
• 20:36For the second line,
• 20:37so I'll just say for a moment
• 20:39that most of these patients you
• 20:42know 60 to 80% response rate.
• 20:44The vast majority of these patients
• 20:47will respond to to treatment,
• 20:50and the tumor often will melt
• 20:52away relatively quickly.
• 20:54Patients go back to work.
• 20:55I saw one guy. Who?
• 21:01Was in the hospital.
• 21:02Went back to work after his first cycle.
• 21:04I just saw him last week doing really well.
• 21:08It's it's really remarkable.
• 21:10However,
• 21:11if these patients have
• 21:13extensive stage disease,
• 21:15they will recur.
• 21:19Unfortunately and so then and
• 21:21and typically when they recur,
• 21:23their disease is much less responsive.
• 21:27If they recur within three to six months.
• 21:32If they, if they make it
• 21:34past three to six months,
• 21:36then they're they're platinum sensitive,
• 21:38and then sometimes we'll
• 21:40retreat with platinum.
• 21:42If they're less than three months,
• 21:44than they're really sort of refractory
• 21:46or resistant, and then we need
• 21:48to really look at other agents.
• 21:50So what other agents are there?
• 21:53Well, lerber Nectin is a
• 21:55standard is a chemotherapy,
• 21:57and this was approved it in June of 2020,
• 22:01based on a small trial.
• 22:03100 patients overall response rates 35%.
• 22:07OK, so this is something that we use.
• 22:11I I note this because again,
• 22:13this sort of gives you a sense of
• 22:15how the how the the the approval
• 22:18space works here so pembrolizumab.
• 22:21And Neevo actually were approved in 2018
• 22:25and 2019 on the basis of very small trial.
• 22:28So 8300 patients and a limited response rate.
• 22:32Wow, just 12%,
• 22:33but that was approved at that time.
• 22:37And and So what you'll see is that.
• 22:41The these two drugs actually now have
• 22:44been withdrawn by the FDA actually
• 22:46withdrawn by from the sponsors because
• 22:49they had subsequent phase three trials.
• 22:51So randomized phase three trials
• 22:53that did not show up a benefit
• 22:56so they actually pulled those.
• 22:58So right now Rubberneckin and
• 23:00Topotecan are the only approved agents
• 23:03for relapse disease and that's why
• 23:05we're trying so hard in this space
• 23:08to to improve options for patients.
• 23:12OK, I'm just going to a few more slides left.
• 23:14This is something I wanted to talk to you.
• 23:17This is a.
• 23:19This is actually a slide about
• 23:22EGFR or non small cells,
• 23:24so the idea being that you
• 23:27have one tumor type.
• 23:29So for example non small cell lung
• 23:31cancer and then depending on the
• 23:33mutation you have you you have
• 23:36different treatments available.
• 23:38So this is something that's now
• 23:40being looked at in small cell
• 23:42and it's not a gene mutation,
• 23:45but it's sort of a a molecular
• 23:48subtype that's characterized by.
• 23:50Overexpression of a transcription factor,
• 23:52so it is something that potentially
• 23:56could be tested for in tissue or in DNA,
• 24:00RNA, and,
• 24:01but that that same idea that you
• 24:04might have different patients.
• 24:07With small cell lung cancer,
• 24:09but a different type that would either
• 24:12respond to a treatment a for the green type,
• 24:16treatment B for the red type,
• 24:19et cetera.
• 24:20That is something that we're
• 24:22starting to look at.
• 24:23It's very far away from any kind of any.
• 24:26Actually,
• 24:26we just started thinking about putting
• 24:28a a trial like this together and swap,
• 24:31but it's very far away,
• 24:33but I think that the best,
• 24:34the that's the promise of being able to take.
• 24:37Small cell biology.
• 24:38Understand it better and and hope
• 24:41to to be able to do precision
• 24:43medicine for those patients.
• 24:47Umm? This is the small cell program,
• 24:51so we see about 80 to 90 patients annually
• 24:55in the in the entire state and Rhode Island.
• 25:00These are our scientists that we work with.
• 25:02Kurt Schaefer is Co investigator on
• 25:06the biomarker EPI Nebo trial that I
• 25:09have and we just put in an abstract
• 25:12ASCO for results on that Katie.
• 25:15Plenty is. I'm working with her
• 25:20to look at what are the mark?
• 25:23What are the the factors in acquired
• 25:25immunotherapy resistance and how can we
• 25:28understand that this is a New Scientist?
• 25:31Doctor Ozier he's coming from Fred
• 25:33Hutch that works on small cell.
• 25:35He's starting this month.
• 25:38And Anna works in Katie's
• 25:40laboratory to do some of the.
• 25:45Some of the. Tissue.
• 25:49Collection and analysis, and this is
• 25:53a resident that's working with me,
• 25:56but I would actually put many of you
• 25:58or most of you on this slide as well,
• 26:00because you're helping in getting those
• 26:03patients accrued to the study and.
• 26:07And the equally important,
• 26:08I'm going to have to get a slide with
• 26:10everybody's picture on it. Melanie, Jen.
• 26:12We'll have to work on that. Umm?
• 26:16So these are the key. Take home points.
• 26:19Combination Chemoradiation is recommended
• 26:21for slime therapy for limited stage.
• 26:24That means limited to a
• 26:27radiation portal combination.
• 26:29Chemo and immunotherapy.
• 26:30This is through the system.
• 26:32Through the blood is recommended for slain
• 26:36treatment for extensive stage small cell.
• 26:38Some selected patients with early
• 26:40stage small cell can benefit
• 26:42from surgery and then followed by
• 26:45chemotherapy and didn't spend a lot of.
• 26:47I didn't spend time talking about that,
• 26:49but that is a possibility.
• 26:53And advances in small cell biology
• 26:55will hopefully yield biomarkers to
• 26:57direct and personalized treatment,
• 26:58and that's something that we're working
• 27:00on actively here to understand.
• 27:02So I did that as my last one.
• 27:07OK.
• 27:09Let's see some questions here.
• 27:12When you mentioned if the patient impatient,
• 27:15you could give them chemo alone and Oh yeah,
• 27:18that's the question that I answered before.
• 27:23What do I know and that?
• 27:24Do you have any questions?
• 27:26Does this make sense to you?
• 27:27Is this similar to other other?
• 27:31Other presentations.
• 27:34I have no questions right now.
• 27:37Is it helpful to hear about it?
• 27:39Yes, very helpful.
• 27:41OK, so like every bit I hear about
• 27:43the different cancers is helpful.