PARP Inhibitors in Ovarian Cancer - Episode 3

Rucaparib in Platinum-Sensitive Ovarian Cancer

Matthew A. Powell, MD:The ARIEL2 study was a randomized trial for patients after 2 prior platinum-based chemotherapies—and they might have had as many as 3—randomized to either placebo or rucaparib at 600 mg bid. And these are patients who either had a complete response or a partial response to their second platinum therapy. And, again, this group enrolled 3 different cohorts: the patients who had a germline mutation or a somatic mutation, a group that had a homologous recombination defect, and then a wild type group. These were all analyzed in a nested manner, and each of those cohorts, as you evaluate that, were statistically significant and showed benefit for all groups included.

The strategy for maintenance therapy for ovarian cancer is relatively new to us as far as routine practice. We’ve been investigating maintenance therapy in ovarian cancer for 20-plus years, and now we have drugs that are actually well tolerated and able to be utilized in this population. So when deciding on a maintenance PARP inhibitor, I think we can turn to studies like ARIEL2 to help inform us that the patients have good activity with manageable toxicity.

So, the ARIEL trial that led to approval of rucaparib in the maintenance setting just in the past month was, again, the large randomized trial showing the maintenance strategy of a benefit for these patients with very impressive hazard ratios of anywhere from 0.2 to 0.4, depending on the population that was investigated.

Other rucaparib studies are also looking at combinations with PD-1 inhibitors, with antivascular agents. I think we have quite a few exciting things in store for the PARP inhibitors.

Transcript edited for clarity.