Targeting PSMA in Prostate Cancer Treatment - Episode 10

Therapy Sequencing and Patient Selection in Prostate Cancer Treatment

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Experts share their thoughts on sequencing hormonal agents and patient selection for clinical trials.

Alicia Morgans, MD, MPH: Ulka, from your perspective, when you’re trying to sequence these agents, given the data as Tanya just pointed out, there are compelling data in this space for cabazitaxel and this interesting PFS [profession-free survival] benefit to treatment with lutetium compared with cabazitaxel. What do you think about sequencing these agents?

Ulka Vaishampayan, MD: A few of the points that came up from CARD are very important. The most important thing is not to use 2 hormonal agents back-to-back and interspersed chemotherapy or some other mechanism of action in between. Clearly, cabazitaxel showed an improvement compared with second hormonal therapy.

With the TheraP trial, we learned how to better select patients who would benefit the most from PSMA-lutetium in my opinion, as well as based on the FDG [fluorodeoxyglucose] findings. If there are only FDG findings and no PSMA [prostate-specific membrane antigen] uptake, that’s also critical information because it tells you that most likely, PSMA-lutetium may not be as effective. It may be time to go to chemotherapy or carboplatin-based if there are neuroendocrine features in this tumor, etc.

Both studies are very important, even though they’re smaller phase 2 studies—[they are] giving us much more insight into the scheduling as well as the better clinical application of these treatments. Then there’s the issue of genomic testing and germline testing to look at patients with DNA-repair mutations, where we have a fairly effective therapy option available with the PARP inhibitors.

Alicia Morgans, MD, MPH: Thank you for bringing in other options. We don’t have time to review every trial, but we shouldn’t forget that there are other agents, including PARP inhibitors and pembrolizumab, for patients who are MSI [miscrosatellite instability] high. These are also options for many of our patients, and we should absolutely keep them in the front of our minds as we’re trying to help patients choose.

Phil, I’d love to hear your perspective. We’ve talked about patient selection. Ulka just mentioned it again, but it’s important for things like lutetium-PSMA-617. It was done differently in the VISION trial vs TheraP. What are your thoughts on patient selection? Yes, we can give kudos to the team from Australia for putting together that nicely sensitive and specific assessment that led us to this population for TheraP. But is that something that’s going to be pragmatic when we’re trying to apply it in the clinic?

Phillip J. Koo, MD: That’s a great point. I’m a little less bullish, especially in the United States, with regard to all this additional imaging, though I’m an imager. You guys have all dealt with preoperatives and trying to get 1 PET [positron emission tomography]–CT approved from 1 patient. Imagine trying to get 2 in a 1-week period and then trying to access a PET-CT and get those 2 read in a timely fashion so you’re not delaying care. It’s challenging. No. 2, 13% of patients in VISION were only PSMA, so it’s a matter of perspective. Is 13 a lot? Is 13 a little? Who knows? There’s a trial, I believe through Alliance [Foundation], that doesn’t include PSMA imaging before you enroll in the trial. I don’t know the specific details, but that opens up this idea that maybe there are patients that will still benefit from this radiopharmaceutical that targets disease due to cross effect, cross talk, or whatnot without having all this imaging. Even with all this imaging, it’s still too early to be close to being able to say what the appropriate cutoffs are and how we define discordance. This shines a little light into this area, but it’s way too soon to come to any conclusions.

Alicia Morgans, MD, MPH: Thank you so much. That will conclude our patient case.

Transcript edited for clarity.