Clinical Cases in Advanced Prostate Cancer - Episode 17

Case 2: Promising Agents and Combination Therapies for Advanced Prostate Cancer

December 21, 2020
Targeted Oncology

Experts in genitourinary oncology share their excitement for promising emerging agents and combination therapies for advanced prostate cancer in the coming years.

Jorge A. Garcia, MD, FACP: Thank you, Mary-Ellen, for an excellent review of those important trials. Perhaps I can get 1 final thought for faculty as to when you look at the movement that we have seen in patients with castration-resistant disease and the many agents we now have approved, recognizing that we don’t understand the ideal sequence to some extent. We do have the PROfound and CARD data. But certainly, there are still limited options for our patients with metastatic castration-resistant prostate cancer. Maybe each of you can give me a final thought about where you see the field moving toward in the next 2 to 5 years with regard to new agents and new combinations. Mary-Ellen?

Mary-Ellen Taplin, MD: We’re all very interested in the FDA’s decision expected next year on PSMA [prostate-specific membrane antigen] lutetium. I had patients on the phase 3 trial who did quite well, even though they were at a very advanced stage of their disease. Radiopharmaceuticals are going to get a lot of attention in the coming years. There are many companies that are developing radiopharmaceuticals, and they have potential to show great palliative benefit and life-prolonging benefit for our patients.

Jorge A. Garcia, MD, FACP: Great. Patrick?

Patrick G. Pilié, MD: Yes, absolutely. With the advent of precision medicine in daily clinical practice with prostate cancer, it’s all about extending the benefit of these targeted agents to a broader population. We can do that through combination therapies such as combining AR [androgen receptor] signaling-directed therapy with DNA damage repair inhibitor therapy, as well as immuno-oncology. Trying to move beyond prostate cancer being an immune-exclusive or immune-resistant cancer, by using combinations to activate the immune system and hopefully provide more durable benefit for patients with metastatic castration-resistant disease.

Jorge A. Garcia, MD, FACP: Great. Ganesh, I’d love to pick your brain. Where do you see yourself as a urologist in the context of advanced disease with patients who still have their primary tumor in place?

Ganesh V. Raj, MD, PhD: I think the question is, “What do you do with a primary tumor?” A lot of this says that it could be an immunologically privileged site. Should you treat it? I don’t know what the answer is. A clinical trial clearly would help answer that. For me, the big emerging agents that are coming are the radiolabeled PSMA, the PROTACs [proteolysis targeting chimeras], the better AR-targeting agents, using more precision therapy approaches, and more of the radiolabeled antibody-drug conjugates. As we go forward, those things would really make a difference in advanced prostate cancer.

More and more, 1 of the key things we’re finding is if you bring these drugs earlier to treat patients with nonmetastatic disease, you’re going to see a much more dramatic difference. With all these drugs—enzalutamide, abiraterone acetate, apalutamide with darolutamide—in the metastatic setting, we saw a 3-month improvement in survival. All of a sudden, we’re seeing 24-month and 26-month improvements in survival. You’re seeing much more dramatic improvement in survival with earlier onset of these drugs. As a urologist, I’m more looking forward to these drugs being used in the neoadjuvant space and more used in the adjuvant space rather than only in the metastatic setting.

Jorge A. Garcia, MD, FACP: Great. Thank you for that, Ganesh. We hope you all enjoyed this Virtual Tumor Board® presentation from Targeted Oncology™. I want to thank my colleagues and friends—Dr Raj, Dr Pilié, and Dr Taplin—for an outstanding presentation and a rich and informative discussion about the management of metastatic castration-resistant disease and also nonmetastatic castration-resistant disease. To our viewing audience, we hope you found this presentation useful and that we have provided you with practical information to bring back to your daily clinics. Thank you. Stay safe. Thank you very much.

Transcript edited for clarity.