GU Cancers 2021 | mCRPC: the importance of genomic profiling

I don’t know that I even mentioned that another poster we had was a really nice gene by gene analysis from the PROfound trial looking at the proper role for olaparib based upon HRR mutations. And so, to your question, Charlie, if you’re not testing, if you’re not getting a molecular and genomic profiling, you would be at a loss to now consider a PARP inhibitor for some patients who have HRR mutation. And we know that upwards of 30% of our patients with mCRPC have one of the 14 HRR mutations that have been listed as, in the labelled indication of approval by FDA in the US, they’re, it’s certainly mostly driven by BRCA2. But in our gene-by-gene analysis, we looked at the prevalence also of all of the less prevalent genes.

I guess to really answer your question is we need to be testing and we need to have a really good understanding in our clinics of both germline testing, testing gene alterations that have been inherited from your parents. But also, that doesn’t always tell the entire story. Because if a germline testing is negative, there can still be somatic positivity for patients with more advanced disease. And that can be interrogated from the tumor itself, from archival prostate biopsy or prostatectomy specimens, or liquid based testing. And it’s not just about the HRR mutations, but again, it’s looking at for clinical trials, P10 loss and also microsatellite instability high. These are all opportunities for us to not only enroll patients in trials, but there’s the tumor agnostic indication for patients who have MSI high, who would benefit potentially from a checkpoint inhibitor.

The testing and the molecular profiling, particularly in our neuroendocrine poorly differentiated cancers, the ones of the really, who really challenge us, perhaps there will be some additional findings from RB1 loss in combination with some of our other molecular analyses. Whether it’s chromogranin A or other molecular lab tests, will help us better serve patients, whether it’s in clinical trials or newly approved indications both by FDA, EMA and throughout Asia and Latin America and the middle East. The world of testing is upon us and it’s a great thing because it helps us to better personalize, tailor therapy, as opposed to thinking of our treatments as a one size fits all.