Decision-Making When Considering ADT and Doublet or Triplet Therapy for CRPC

In a roundtable moderated by Tanya Dorff, MD, of City of Hope, panelists Michael Morris, MD, of Memorial Sloan Kettering Cancer Center; Benjamin Garmezy, MD, of Sarah Cannon Research Institute; and Yu-Wei Chen, MD, MS, of the University of California, San Diego discuss new treatments and therapy considerations in the field of castration-resistant prostate cancer.

In the second part of this series, the decision-making process of considering androgen deprivation therapy and doublet or triplet therapy for CRPC is examined.

Watch part 3 of this series: Discussing New Game-Changing Studies in Prostate Cancer

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Dr. Dorff:
Well, we’ve talked a lot about imaging. What other patient or disease characteristics really factor into your decision-making when you’re starting upfront ADT with doublet or triplet?

Dr. Chen:
Yeah, so I think nowadays, I tend to send NGS panel to learn a little bit more about the molecular profiling at a home or a sensitive setting. So for example, like high-risk features, P10, RB1, or p53 mutations. There is a dataset suggesting using a doublet chemo agents in a patient who is ADT and LRSI to really try to treatment specification in this most populations knowing that the trial is based on a phase two study. And I think mostly conduct in a castration-resistant setting. But I think certainly, the molecular profiling offers some information to guide the discussions with our patients, how we would like to achieve the goal in terms of prescribing the treatment arrangement for them.

Dr. Dorff:
So NGS definitely sounds like an important tool. What other patient factors or disease factors?

Dr. Garmezy:
I mean, it’s NGS, right? It’s age and you bring up some of them, but we also know BRCA mutations and can also be poor prognostic indicators that would sway your decision, may not make your decision. Age is also critical, right? What’s the runway of the patient’s expected lifespan? Where is the metastatic disease, right? We’re going to treat liver lesions different than we’re going to treat bone lesions or nodal disease. So I think a lot of these factors are at play. I actually sometimes will think, yeah, well, what’s the Gleason, right? I mean, a Gleason 7 that’s metastatic is probably going to behave different than a Gleason 10 that’s metastatic. That’s going to be tilted towards androgen resistance much more quickly.

So all of these things come into play and sometimes looking at even the architecture of the original prostate biopsy, is there some kind of variant instead of a traditional adenocarcinoma there that is going to be a little bit more of a bad actor comes into play. So I think it’s complicated, it’s nuanced, and ultimately whenever things don’t look as they should, that’s when I’m starting to think about providing a taxing, again, like also metastatic with very low PSA, right? These types of things.

Dr. Morris:
I think that I was really impressed at ESMO with a very elegant analysis of STAMPEDE by Decipher as additional information to be used in the decision-making as to who should get triple therapy. I have not ordered enough Decipher. And indeed, I think that NGS can sort of sometimes fool you because NGS doesn’t tell you. It tells you who’s going to do well and who’s going to do poorly, but not whether what you do is influencing that. And this analysis from STAMPEDE has informative information in terms of the relationship between Decipher treatment and outcome.

And also, it surprised me because usually we think of prostate cancer as a very dynamic disease and that you always have to do sequencing on the most current metastatic disease and the most current clinical state. Of course, Decipher goes back to the primary. And so, that seems like ancient history and yet the inception of the tumor in terms of this RNA signature, that Decipher is is quite useful in the metastatic setting in terms of who should get additional treatment or not. So I think I will change practice on the basis of that, at least in those patients that I’m considering for intensified treatment with chemotherapy and use Decipher.

Dr. Garmezy:
Yeah, I think that’s a great point. That data set was interesting and it also makes sense because all these other things that I just mentioned are clinical surrogates of what the actual biology of that tumor is when that is actually getting more into the direct biology of the tumor. So I do think it’s interesting. I mean, I guess, are you implying that it’s time for us in the community to start ordering Decipher for all of our patients?

Dr. Morris:
It’s not just in the community, us medical oncologists everywhere. We have not the primary users of Decipher.

I think we haven’t been leveraging a valuable, easily available and resulted tool that we should be. This goes across the clinical context of practice into sort of like a field deficit, so to speak, that we’ve… At least the urologists that I know have been ordering a lot more Decipher than the medical oncologists. And I think we need to rethink our paucity of looking at Decipher scores.

Dr. Dorff:
Well, this was the first analysis moving Decipher into a metastatic population. Previously, it’s really been validated in the localized, and it has been so well validated that these prospective trials like NOGGO 9 for high-risk localized disease receiving radiation are using it to stratify for intensification or de-intensification. And I think it was really groundbreaking that presentation at ESMO this year in the context of Docetaxel in particular because they’ve been doing these signatures kind of behind the scenes for a long time, trying to tease out who might respond better to different types of therapy. And they give you luminal basal now also. So very interesting information.