Dr. Ross on unmet needs with PARP inhibitors in prostate cancer

In this video, Ashley E. Ross, MD, PhD, discusses remaining questions with PARP inhibitors in the prostate cancer treatment paradigm. Ross is an associate professor of urology at Northwestern University Feinberg School of Medicine in Chicago, Illinois.

Video Transcript

There's a lot of questions; there's multiple trials going on in the hormone sensitive metastatic setting. Can you move those up into that setting earlier? So instead of waiting till someone has progressed into castration resistant disease, is there a benefit for moving up to earlier setting? I think there may be benefit there. The PARP inhibitors can cause cytopenias, particularly anemia as an [adverse event] and it could cause some GI side effects as well. Long-term, there's a worry for myelodysplastic syndrome and other types of hematological malignancies that could arise after long-term PARP use. The question there will become, in the hormone sensitive setting, what's the correct duration of therapy, particularly the response has been fairly profound.

In the castrate resistance setting, there's been some look at combinational therapies using androgen signaling blockers and PARP inhibitors together. There's still some uncertainty there of if people are getting those agents in the hormone sensitive setting, meaning if we start out as we should for most people with advanced prostate cancer hormone sensitive by using at least 2 agents – some type of androgen deprivation therapy and then some sort of antigen receptor signaling inhibitor – do they benefit from the continuation of those agents in the castrate resistant setting? Those are some of the regimens that were put forward in trials like PROpel and MAGNITUDE, etc. It's very unclear or rather to just get 1 agent, plus their ADT in the CRPC setting, which I think most of us are gravitating to. So, a lot to be done in terms of moving PARP inhibitors earlier. Is that safe? Where do we get the most bang for our buck? And does the therapy have to be indefinite? Using them in the castrate resistant setting, we know it works for BRCA 1, BRCA 2, can we tease out other members where it's going to also be impactful? And a lot of work, actually a huge volume of work, that has to be done with figuring out who is going to have [more] or less toxicity to the PARPs? As I mentioned, some people will have pretty profound anemia and need transfusions, there can be GI side effects. If we can figure out who's going to have less side effects and get more efficacy, then that's where we have to head.

This transcription has been edited for clarity.