Targeting PSMA in Prostate Cancer Treatment - Episode 12

Lutetium-PSMA-617 and Novel Agents in Prostate Cancer

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Oncologists share some final thoughts on lutetium-PSMA-617 and novel agents to look out for in prostate cancer treatment.

Alicia Morgans, MD, MPH: At this point, we can ask some closing questions to each of our panelists. We’ll start with Phil. Could you summarize your thoughts on the use of lutetium-PSMA-617 in the metastatic castration-resistant prostate cancer setting? What do you think about patient selection and that treatment in general, when we think about this patient population?

Phillip J. Koo, MD: It was such an exciting day when you heard the announcement. Obviously, there was so much excitement around this, especially after the data were presented at ASCO [American Society of Clinical Oncology Annual Meeting] in 2021. Treatment and patient selection are still going to be determined and will continue to evolve. As our skill and ability to home in on certain questions improves, we’ll be able to answer that better. In the meantime, we need to be prepared and find ways to access this drug for our patients. Whether you’re in a purely private practice, an integrated health system, or an academic health system, there’s a path forward to make sure you can get your patients access to this through either nuclear medicine or radiation oncology. On the operational side, it’s easy. It requires a little work up front, but once you have it down, it can run like a well-oiled machine. In the end, you need champions. You need champions on the ordering side and on the administration side. I have no doubt that with those components, anyone can get this up and running.

Alicia Morgans, MD, MPH: That’s a very encouraging message, Dr Koo. Let’s hear from you, Tanya. What do you think?

Tanya Dorff, MD: We still have some to learn about patient selection. We need to do the work because when we have multiple options, we want to have our patients access as many options as possible. But we also want to pick what’s going to be most effective earlier on and spare the health system the cost of choosing a treatment that’s going to be ineffective and spare the patient the potential adverse effects if it’s not going to work for them. With the 2 patient selection criteria from VISION and TheraP and from other work that’s being presented and ongoing, hopefully we’ll start to get some ability to individualize and say if this is a patient who’s better off with radium or with chemotherapy or this 1 is going to have a tremendous benefit from the lutetium-177. That’s what I’m looking for in further studies. Also, combinations will be really exciting. There’s interest in combining radiopharmaceuticals with immunotherapy. Hopefully, we can improve on this exciting new treatment option even further.

Alicia Morgans, MD, MPH: Ulka, what are your thoughts on lutetium-PSMA-617?

Ulka Vaishampayan, MD: Having treated patients on the VISION trial, I’ve been very excited about the efficacy of this agent and the tremendously tolerable toxicity profile. That makes me motivated to consider this therapy option up front in metastatic castration-resistant disease. Especially if we use triplet therapy or docetaxel increasingly in the frontline metastatic hormone-sensitive setting, it becomes even more important to immediately test patients with PSMA [prostate-specific membrane antigen] PET [positron emission tomography]scans when they turn castration-resistant and consider this therapy.

There are other advances you have to keep in mind. There are multiple exciting agents in the field that should be looked at, and clinical trials should be at the front of our minds when we consider treatment options for our patients. Then use second-line chemotherapy and genomic profiling, because if you find a targeted therapy that fits that patient’s genomic germline genetic profile, that’s another thing to consider up front in the metastatic castration-resistant setting.

Alicia Morgans, MD, MPH: Let’s go back to each of you. Think about what type of therapy you’re most looking forward to learning more about in this setting. Ulka, you’re leading a phase 1 program, so I’m sure you’ve gotten a lot of exciting molecules. What are you most excited about moving forward?

Ulka Vaishampayan, MD: Immunotherapy advances and cellular therapies are very exciting in the prostate cancer field, mainly because they hold the promise of long-term remissions with the treatment. On the flip side, there are AR [androgen receptor] degraders. We haven’t seen the last of tackling AR access in advanced prostate cancer, so that branch of treatment is also looking very promising.

Alicia Morgans, MD, MPH: Tanya, what are your thoughts?

Tanya Dorff, MD: You’re probably aware that I’m a big fan of immunotherapy and, in particular, cellular therapeutics. Having a live treatment that can adapt as the immune system can as the cancer evolves is an advantage, and we believe it will get us to more durable remissions that patients are seeking. Of course, there are toxicities there that need to be managed and worked out, but there’s such a versatile platform. When we think about how some patients don’t express PSMA and wouldn’t have been included in the VISION trial, those patients are a real unmet need. Immunotherapy potentially could fill that gap by studying some novel targets.

Alicia Morgans, MD, MPH: I had a feeling you might say that. Phil, last but not least, and you’re welcome to focus on those options or the exciting new radiopharmaceuticals that are also coming down the line.

Phillip J. Koo, MD: It will come as no surprise that I’m a big fan of radiopharmaceuticals. It’s clearly been shown that radiopharmaceuticals can be safe and effective with the approval of radium-223 and now lutetium-177-PSMA. Obviously, there’s a lot of work being done with other radiopharmaceuticals, particularly alpha particles such as thorium or actinium. It will be very interesting to see what happens with that. Tanya talked about this earlier, but the combinations are where there’s a lot of potential as well. It will be exciting to see a lot of the work from you guys, who are so effective in this space, finding different ways to put things together and get that synergistic effect.

Alicia Morgans, MD, MPH: Thank you all for your thoughtful case presentations and informative discussion. To our viewing audience, thank you for joining us for this Targeted OncologyVirtual Tumor Board® presentation. We hope today’s discussion was a valuable use of your time and that you acquired practical knowledge that can help you in your clinical practice.

Transcript edited for clarity.