Practical Considerations in Selecting Therapy for Metastatic CRPC


Closing out their discussion on prostate cancer, expert panelists highlight which factors best inform selection of therapy for patients with mCRPC.


Evan Y. Yu, MD: Let's bring it back to relevance to this case. This patient has received abiraterone and has received docetaxel. We didn't forget the case; we have to bring it back to this. This patient has a lot of options available. I'd love to hear what each one of you would think about the situation and what you would treat this patient with.

Pedro C. Barata, MD, MSc: We saw data today about a fact of prior therapy. We got data with radium, and we got data with chemotherapy. We got data with prior NHT's. If this patient had harbored a BRCA-2 I probably would make the case to consider a PARP inhibitor first. With that said, it would not be wrong to do the other way around. The reason why I would do that is because if you follow the data, you've used lutetium in the later stage with the data you have to be considering olaparib for instance because it was developed earlier in the pre-chemotherapy. The other piece I would like to highlight is the safety profile of lutetium is very favorable. However, it's interesting because what I take from cabazitaxel is a pretty active agent number 1. Number 2, within difference in overall survival and also that the absolute numbers in terms of median PFS [progression free survival] were identical in GU 5.1 or 5.2 months. What is different is the tail of the curve, which suggests that not everybody is the same and tumor plays a role. The other piece of the story is, I am going to offer lutetium PSMA to everyone regardless of a PSMA scan. I just want to remind, for instance in vision about 82, 84% of patients were eligible by scan, which means almost 2 out of 10 patients will be ineligible. If you don't have the target, then the chances of that drug to work are not obviously the same as for folks who have the target. For lutetium I do consider the scan, which might be or might not be available right this second and impact will decide. But that's an important point. I don't think we have enough data to decide between target therapy PARP inhibitor and a PSMA in that scenario. In that case you could also consider rucaparib because in this patient it is post docetaxel. We could do olaparib, rucaparib.

Evan Y. Yu, MD: Let's say this patient doesn't have a DNA repair alteration. Let's keep it simple. Mary Ellen, are you going to give this patient lutetium or are you going to give this patient cabazitaxel?

Mary-Ellen Taplin, MD: I'm going to give him PSMA lutetium.

Andrew J. Armstrong, MD, MSc: It depends on the results of the PET.

Mary-Ellen Taplin, MD: Yes. It's based on the PET.

Andrew J. Armstrong, MD, MSc: If you tell me FTG is positive and PSMA is negative, my answer is the opposite.

Pedro C. Barata, MD, MSc: Or if you have to-To his point, if you see disease-and this patient has visual disease, right? Let's say he progresses liver mets. I'm not as excited with lutetium as I would be if node only or node with some lungs for instance. Because we have this thing called tumor heterogeneity which you might or might not be capping the PSMA. And that seems like the outcome of patients it's different depending on their location of mets. That's probably a patient where we bring to the prior discussion, which genomics on top of it. No longer you would be considered in comazi but maybe you actually are going to bring platinum revision to that. Everybody will get lutetium ahead of cabazitaxel. The patient and the disease characteristics and profiling, molecular profile will help us a little bit better about who gets what.

Tanya B. Dorff, MD:I'm just going to state the obvious, which is that of course we would all be looking for a clinical trial opportunity. We always want to line up as many options as possible for patients. Cabazitaxel is not going anywhere. Lutetium PSMA is not going anywhere. If we have great trial eventually that patient will have the most options. None of these drug’s cure. We need more options for patients. And it's always the right time to think about a trial.

Evan Y. Yu, MD: One thing we haven't talked about is immunotherapy. Tanya, immunotherapy options for our patients with metastatic castration-resistant prostate cancer. Would you ever consider in this patient?

Tanya B. Dorff, MD: On clinical trial. Or if he had microsatellite instability or very high tumor mutation of burden which can be used to select patients for pembrolizumab immune checkpoint inhibitor therapy. But I think otherwise should really be done on clinical trial.

Evan Y. Yu, MD: Not the ideal SLT candidate here.

Tanya B. Dorff, MD: No.

Evan Y. Yu, MD: Just to wrap up. I just want to take a broad picture overview on metastatic castration-resistant prostate cancer. You have somebody with new first line mCRPC. Pedro, just march us straight down. We don't have a lot of time left but just march us straight down. What do you do first? What are your considerations for second, third, etc.?

Pedro C. Barata, MD, MSc: I have a patient in front of me. I take several factors into consideration. Some are totally patient. Others are physician driven. It matters to me how far he is from my center. It matters to me the social support. It matters to me the prior therapies of the patients. He has been exposed to, the hormones space. It's different if the patient got Doce ADT versus a patient who got ADT alone and is now progressing to cRPC. It matters to me the location of the metastatic disease. It matters to me if I have tissue available and I can prove the point that he is a bread and butter adenocarcinoma of the prostate versus features are small cell. It matters to me the PSA. The absolute number. It also matters to me the genomic data available.

Evan Y. Yu, MD: What you're saying is there's no one sequence.

Pedro C. Barata, MD, MSc: No one sequence. We have a list. A big list of therapies available and the question is, what's the secret sauce. I don't think there's one secret sauce. We all try to make all this make sense. But there's-now, saying that the real-world data suggests that most patients get an NHT followed by still an NHT. Some are getting a chemotherapy. Over time we'll see an uptick of things like lutetium PSMA, an uptick in things like PARP inhibitors. Perhaps obviously other therapies. But I think that's where we are today.

Evan Y. Yu, MD: Let's go ahead and wrap up. I want to thank you all 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. Have a wonderful day.

Transcript edited for clarity.

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