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Yale Cancer Center scientists present promising approaches for treating advanced prostate cancer

September 30, 2019

Each year around the globe, an estimated 1.3 million men are diagnosed with prostate cancer, with more than 350,000 dying of the disease. Yale Cancer Center and Smilow Cancer Hospital scientists reported promising updateson two clinical trials studying new treatment approaches for patients with advanced prostate cancer. Daniel Petrylak, M.D., professor of medical oncology and urology and co-director of the Signal Transduction Research Program at Yale Cancer Center, presented the findings today at the European Society for Medical Oncology (ESMO) conference in Barcelona, Spain.

The first highlight reviewed KEYNOTE-921, an international phase 3 clinical trial that began in June and combines chemotherapy along with immunotherapy. Eventually running in 31 countries, KEYNOTE-921 will enroll 1,000 castration-resistant metastatic prostate cancer (mCRPC) patients whose disease has progressed after treatment with the hormone agents enzalutamide or abiraterone acetate and who have not been treated with chemotherapy.

The randomized, double-blinded study will evaluate the efficacy and safety of pembrolizumab, a checkpoint blockade immunotherapy approved for many other forms of cancer, combined with the chemotherapy docetaxel, along with the anti-inflammatory agent prednisone. KEYNOTE-921’s primary endpoints are overall survival and progression-free survival measured by radiographic imaging.

“Our thought is that by inducing cell damage with chemotherapy, you may be sensitizing the immunotherapy to see tumors more clearly,” Petrylak said. “Some preliminary clinical data suggest that this may produce more activity by the immunotherapy, but we need a randomized trial to prove that.”

In the second update, Petrylak reviewed results from a phase 2a trial that suggested that treatment for mCRPC patients may be improved by combining targeted radiation therapy with approved drugs.

This trial is an open-label study among 63 mCRPC patients with bone metastasis. The trial examined efficacy and safety with radiation therapy using radium-223, an agent that binds to bone areas that are altered in metastasis, either given by itself or in combination with enzalutamide or abiraterone acetate plus prednisone.

The study’s primary endpoint was shrinkage in bone scan lesion areas after 24 weeks. About half of patients receiving the combined therapies achieved this result, compared to about a quarter of patients given radiation therapy alone. According to Petrylak, the researchers did not find a correlation between bone scan lesion areas and overall survival, mainly because the trial was small and did not continue long enough to measure median overall survival. The trial was not designed to compare results from the two combination treatments.

Although patients in the combination arms experienced more treatment-related adverse events than patients in the monotherapy arm, the trial did not suggest any new safety signals for the drugs. “There's been some controversy about combining radium with agents such as abiraterone acetate and enzalutamide because of increased fractures in people with mCRPC, but we found there was a lower fracture rate in the combination arm, which was a little bit unexpected,” Petrylak said.

“Both of these trials are representative of Yale’s commitment to developing novel treatments for advanced prostate cancer,” he added.

Submitted by Anne Doerr on September 30, 2019