mHSPC: Assessing Patient Response and Selecting 2L Therapy at Progression
Shared insight on strategies to monitor patient response to therapy and select second-line treatment when hormone-sensitive prostate cancer progresses.
Transcript:
Alan H. Bryce, MD: Let’s continue with this case. This patient did go on to receive triplet therapy. We threw a curveball here, we’re saying the patient got ADT [androgen deprivation therapy], docetaxel, and apalutamide. Of course, this isn’t one of the clinical trial regimens, and yet this happens. I see patients come into the clinic who received a different antiandrogen [treatment]. Dr Lowentritt, do we think your choice of the partner oral agent matters when giving triplet therapy? Then a second question here, as we look at this case stem, the patient had a really good response. Within 7 months the PSA [prostate-specific antigen] goes from 590 to less than 0.1 ng/mL, the soft tissue disease is much better, and quality of life is much better. What can we tell the patient prognostically about this improvement in the PSA? Is it meaningful, is it something we talk about? What would you tell your patient? Because of course, they’re all very focused on the PSA, aren’t they?
Benjamin H. Lowentritt, MD, FACS: Absolutely. Although this patient was symptomatic, the PSA for most patients is the only sign they’ve ever had that they had cancer. Even when they get to this stage, many of them have never had a symptom, so the PSA remains really important. We have a lot of data now supported by a number of these trials and even some real-world studies that show that the depth of the PSA, how much it falls, is a sign of overall both prognostic and quality of life, it predicts survival. We’re back in that point where PSA is relevant. We want to de-emphasize the PSA on some levels and not create the PSA anxiety. But we know that reaching a PSA of 90 or getting a PSA of 0.2 ng/mL or less both predict better responses from survival and quality of life. When you asked the first question, which is, is there one over another that you would choose, you want to choose the one you’re most comfortable that a patient’s going to be able to take for the longest time period. It’s mostly adverse effect driven. You certainly want to use the best data available when choosing for the individual patient. Whether it’s sequencing or combination therapy, or whatever you find yourself doing, this is an early signal in the first few months that you can help talk to your patients about, and also potentially de-escalate some of their monitoring, which is what I’ve started to do when I have a really strong PSA response. I’m no longer seeing them monthly or every 2 months. I might be seeing that patient every 3 months and giving them a break from the requirements of coming into the office, etc. There’s a lot that can be learned from the PSA still.
Alan H. Bryce, MD: Absolutely, I agree with all that. Dr Zhang, let me ask you this question, when this patient relapses, what do you think of as the treatment options at that point? Let’s say he relapsed today, fast-forwarding, what would you talk about today?
Tian Zhang, MD, MHS: I think a lot about depth of response and then timing of their progression. Can you tell me if it’s within 3 months of finishing chemotherapy, or if it’s a year and a half out?
Alan H. Bryce, MD: Let’s say this is 18 months later, so 4 months of chemotherapy and then another 14 months ongoing with just the AR [androgen receptor] inhibitor.
Tian Zhang, MD, MHS: In those cases, I generally would like to think about rechallenging, potentially with more chemotherapy. In a subset of patients, we might have a trial available for CDK12 alterations. We can think about whether this also portends some susceptibility to our immune checkpoint inhibitors and try to get that off-label. Then in these post-chemotherapy spaces, I’m often thinking also about lutetium, PSMA PET [prostate-specific membrane antigen positron emission tomography] imaging, and if they have PSMA uptake, who is a good candidate for lutetium? In today’s climate, we would be at least rechallenging with the alternative chemotherapy like cabazitaxel before we would do PSMA lutetium, but eventually as we get more information about PSMAfore and other trials, we might be looking at using lutetium in earlier settings.
Alan H. Bryce, MD: Fair, absolutely.
Transcript edited for clarity.
