PARP Inhibitors in Ovarian Cancer - Episode 5
Matthew A. Powell, MD:These patients with recurrent or twice-recurrent ovarian cancerwe know they’re in trouble. They’re not likely to have long treatment-free intervals, especially if they’re coming in or finishing that most recent platinum with a partial response. We know those patients are likely, even if we do a watch-and-wait approach, to need therapy in the near future. One of the things we know is platinum is damaging to DNA. Perhaps PARP—coupling it with the maintenance strategy, giving the PARP shortly after the platinum—may capitalize on that damage that the platinum has performed. So, I think maintenance strategy makes sense. That’s the way a lot of these trials have been run. And I think that as we try to understand a watch-and-wait approach versus a maintenance approach, I don’t think we’re going to see a lot of differences because typically the time that we would watch and wait these patients is just a few months. And perhaps catching these patients when their disease burden is at the least amount is the best strategy.
When we look at selecting patients for maintenance strategies, we would certainly say we have some signals to say who is most likely to benefit most. For our patients with germlineBRCAgene mutations, those withBRCA2really tend to seem to have the most impressive hazard ratios. Coming next are otherBRCAgene mutations, other genes involved in the Fanconi pathway that give us homologous recombination defects. When we see these signals, we know those patients are most likely to have benefit. I think as we learn from Study 19, we even have wild type patients who might benefit. And if we can identify patients who can benefit, they can benefit for a long time. So, I don’t think we know the whole story yet. We thought it was HRD, but it’s certainly more, and it’s beyond that at this time.
Transcript edited for clarity.