PARP Inhibitors in Ovarian Cancer - Episode 2

Rationale for Olaparib in Advanced Ovarian Cancer

Matthew A. Powell, MD:Olaparib was approved in late 2014 for the treatment of patients with germlineBRCA1andBRCA2mutational status, and they had 3 or more prior lines of therapy. This was a very exciting advance for us as a treatment option for our patients with ovarian cancer.

The SOLO-2 trial was a trial for maintenance use of olaparib in patients with germlineBRCA-mutated status. Patients were randomized to receive either placebo or active drug, and these were the tablet form of olaparib. This showed a significantly improved benefit, so highly statistical difference in the 2 groups when we used the maintenance strategy of olaparib.

Study 19 was a study that was done earlier, and it had both wild type andBRCA-mutated patients, and these patients received the capsules of olaparib. It is one of the trials that we have the longest follow-up data in, and we actually see a fairly strong trend toward difference in overall survival in this population. Now, it ended up not being statistically significant, but thePvalue was less than 0.05. But because of multiple data analyses, this was considered not statistically significant. But I think many of us also are impressed by the long tail on the group that received olaparib and the patients who were on greater than 5 years of therapy. And I believe about over one-third of those patients wereBRCAwild type.

So, maintenance olaparib seems to be well tolerated, and I think it’s best noted by Friedlander and colleagues, who did a very, I would say, state-of-the-art analysis when we look at patients being analyzed in a clinical trial and assessing quality of life. And this time without symptoms analysis, or TWiST, was really elegant, I would say, and it really showed us that, yes, there is some detriment to being on these maintenance strategies. But overall, our patients feel well, do quite well, and, even when we adjust for some of the toxicities we’re giving them, seem to have a benefit.

The SOLO-1 trial—we’re still awaiting results on that, but this is an up-front trial looking at a maintenance strategy after primary chemotherapy. We hope to have those data out fairly soon, helping to inform us on patients receiving PARP inhibitors after frontline therapy. For SOLO-3, we hope to have results for that early in 2019. Again, anxiously awaiting those results.

Transcript edited for clarity.