Genetic Testing in Prostate Cancer - Episode 4

Genetic Testing in Metastatic Prostate Cancer

January 8, 2021
Urology Times staff

Angelo A. Baccala Jr., MD: The other important thing is that, for some of our patients who show up metastatic at initial diagnosis, or unfortunately become metastatic while we’re treating them, genetic testing really does help treatment approaches and decides what we’re going to do for them in these patients with advanced prostate cancer. Do you want to talk a little about that, Jason, in terms of what your thoughts are and some trials that maybe have shown some good data?

Jason M. Hafron, MD: Definitely. This is 1 of the most exciting areas of urology right now. The FDA has approved 2 PARP inhibitors for men with metastatic, castration-resistant prostate cancer. When I encounter these patients, I will order somatic and germline testing on all these patients. The reason why it’s so important to do somatic and germline testing is there have been 2 major trials that have read out this past year: the PROfound trial and TRITON2.

PROfound was a positive trial for olaparib. Basically, they compared olaparib in patients who were failing oral oncolytics. For the comparator arm, the patients were flipped to a secondary oral oncolytic, but in the patients who had a homologous recombinant mutation, they were switched over to olaparib. The data are pretty strong that there was a 66% reduction in progression or death. So it’s a very positive trial. Switching patients with homologous recombinant mutations, you can reduce progression and death by 66%. When you look at that trial, you really see the patients with BRCA2 mutations responded very well, and if you pare it down or dig into the trial, you’ll see that those patients pushed or propelled most of the response in the entire cohort.

The other trial was TRITON2. It was a phase 2 trial that looked at rucaparib. Rucaparib is a PARP inhibitor as well. Its end point was objective response rate, and it showed a 44% improvement in objective response rate. The only subtle difference between that trial and the olaparib trial, or PROfound, was that with the rucaparib, patients also had to fail taxane. They had to fail oral, they had to fail taxane, and then they could qualify for the PARP, which is in their label.

Those are 2 major trials that offer a lot of benefit to our patients. In our practice, we have started using PARPs. We’ve been involved in—not these trials, but other trials—looking at PARPs. The safety and tolerability are good, and we can extend life with these patients. It’s very exciting to offer another line of therapy. Again, these patients who qualify for these drugs have to have a homologous recombinant mutation. Olaparib allows about 14, and then rucaparib is BRCA1 or BRCA2.

Angelo A. Baccala Jr., MD: That’s an excellent summary of that. Thank you.