IO Therapy in mCRPC and Clinical Pearls


Before sharing clinical pearls for the treatment of prostate cancer, key opinion leaders reflect on the potential use of immune checkpoint inhibitors in mCRPC.

Alan Bryce, MD:
Dr Lowentritt, immunotherapy [IO] is always a hot topic in oncology; all our patients want it and they ask about it all the time. We’ve had some updates recently about immunotherapy regimens in prostate cancer, can you speak to that?

Benjamin Lowentritt, MD, FACS: Sure. Unfortunately, the conversation is still relatively brief. If we don’t have the tumor agnostic indications, I will say that in the genomic testing and broader genomic testing, you will find those needles in the haystack that have the microsatellite instability or high TMB [tumor mutational burden] and may be good candidates for it. In looking at broader indications for IO therapy, we got recent updates on 2 trials, [including] the CheckMate 650, which was a phase 2 that looked at 2 different regimens of the combination of IPI [ipilimumab] and Nivo [nivolumab] versus an ipilimumab-alone arm and a cabazitaxel arm. There was at least an initial signal for the phase 2 trial that there was maybe some benefit in the combination ipilimumab, nivolumab regimen. I think there’s going to be some follow-up data and a follow-up trial, which is promising. Now, that was a post docetaxel cohort, a later cohort of patients. Then we also heard from the KEYNOTE-921 [study], which was the combination of pembrolizumab and docetaxel for patients who had mCRPC [metastatic castration-resistant prostate cancer] and were otherwise candidates for docetaxel. It was testing whether adding pembrolizumab to docetaxel was a benefit. Unfortunately, that was a negative trial, but there weren’t any terrible safety signals. We at least got some information that the combination remains safe in these patients, although there wasn’t a lot of positive effect on the disease. There are certainly more combinations to come down the road, but that was what we’ve seen recently.

Alan Bryce, MD: Thank you very much, Dr Lowentritt. Unfortunately, it hasn’t worked. No one can say we haven’t tried. We’ve covered a lot of ground here tonight, which reflects how much activity there is in prostate cancer now and how much progress we’re making. I want to thank you all for this rich and informative discussion. Before we conclude, I’d like to get some final thoughts from each of you on unmet needs and future perspectives in prostate cancer. We’ve been going alphabetical, we’ll reverse it. I’ll start with Dr Zhang, and we’ll go from the end of the alphabet here.

Tian Zhang, MD, MHS: Thank you. We’ve been talking a lot about trials and cohorts of patients. As we have more options for our patients, and we are learning more about sequencing these therapies, each life prolonging therapy is meaningful for that individual patient who is able to experience the sequence. In our practices, we’re now having patients live 10 or 15 years with their metastatic prostate cancers. My message is hopeful, I think we are truly getting patients to live longer and hopefully preserve their quality of life at the same time. This is a great problem in mCRPC, and as we have more treatments, we’re tackling more treatment resistance and hopefully designing more rational therapies to tackle those mechanisms. Thanks.

Alan Bryce, MD: Very good. Dr Posadas, how about you?

Edwin Posadas, MD: I have to echo what Dr Zhang just said, because we’re making real progress, and it’s a delight to come into the clinic and have patients asking about opportunities to participate in trials. They see the value in what it is that we’re doing. I’m old enough to remember the days when we were just throwing things up against the board hoping for a signal, and now we’re optimizing, we’re personalizing, and we’re keeping quality of life in mind as an important goal. I think the patients feel that. I hope that others who are involved, both at the regulatory levels and at the pharmaceutical levels, continue to support these important efforts because the strides are being made. There are still a lot of barriers to getting good research done. Each of us feels that in our day-to-day lives, both in the clinic and in our administrative roles, but the commitment from the patients and the doctors for doing this is strong. I think we’re at a big inflection point in the history of prostate cancer that’s going to make the world better for men affected by this disease and their families.

Alan Bryce, MD: I appreciate that. How about you, Dr Lowentritt?

Benjamin Lowentritt, MD, FACS: Just a slightly different spin. I’m the urologist saying this, but we’re learning because we have patients living so much longer. We’re seeing those impacts of what we’re doing for patients on other diseases, on cardiovascular risk, metabolic syndrome, and cognitive factors, etc. It may be that we can’t avoid some of the therapies and we can’t deintensify them, but we’re learning more about what we’re causing, and maybe other ways to mitigate and counsel patients, and to help them look out for things. It’s where I think there’s a lot of unmet need, in helping us to counsel and help our patients avoid some of those long-term consequences, because it is great that we’re able to keep people alive longer. We have this discussion that you’re trying to keep them alive to die of something else. That’s not the best way to think of it, but certainly the reality. Increasingly I worry, is that something else something we cause with our treatments? It’s a challenge we have to face, and one of the next challenges as we get more and more patients on better therapies earlier.

Alan Bryce, MD: Dr Heath, how about you? What are you most excited about and future perspectives here and unmet needs?

Elisabeth Heath, MD, FACP: I’m excited to have participated in this panel for sure. Thanks to all my colleagues and to you, Dr Bryce. I’m really excited about the ongoing conversation surrounding disparity and care. It might be new to some folks, but those of us who’ve been doing it for 20 years, we’re excited that others are participating in this conversation. All these data sets and everything we talked about still is not enough to understand what is happening in the underrepresented groups. We’re OK, but we’re nowhere close to where we need to be. I think it takes all of us to be mindful to try extra hard, spend more time, and increase the visits to encourage men in every level, not just for therapeutic, but registry and genomic trials, in any aspect where they can contribute and be represented. Getting the word out is important. For those of you who work in an NCI [National Cancer Institute]-designated cancer center, or at least are located near one, there are so many new resources now that I’m excited about, the Office of Health Equity, and so many places you could tap that even if you don’t have that resource yourself, please reach out. These conversations maybe a year from now, after the next ASCO GU [American Society of Clinical Oncology Genitourinary Cancers Symposium], will have even greater representation.

Alan Bryce, MD: Thank you for that, you’re absolutely right. It’s a wonderful comment to bring everything together that we’ve talked about this evening. I want to thank the panel once again. To our viewing audience, thank you for joining us. We hope you found this OncLive® Peer Exchange discussion to be useful and valuable to the treatment of your patients with prostate cancer. Thanks very much.

Transcript edited for clarity.

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