PARP Inhibitors in Ovarian Cancer - Episode 6

Sequencing Therapies for Ovarian Cancer Progression

Matthew A. Powell, MD:When we look at how to sequence therapies in epithelial ovarian cancer, it’s not a 1-size-fits-all process. We know patients who do very well with their up-front platinum and taxane, and have a nice treatment-free interval, will likely benefit from that therapy again. We have to consider the results of GOG-213, which was in the first recurrent setting looking at patients who received carboplatin/paclitaxel plus or minus bevacizumab. It was randomized use of bevacizumab. There was also a second randomization in there where there was a surgical question that was asked, making the interpretation a little bit trickier. But it did show a strong trend or maybe even a statistically significant benefit to the use of bevacizumab in that population, kind of building on this experience we had from the AURELIA study showing that the combination of a taxane and bevacizumab was really maybe something special. Traditionally in the past several years, we’ve gotten away from using Taxol (paclitaxel) again at recurrence with platinum, as we were trying to avoid hair loss and neurotoxicity. But I think we have to really challenge ourselves and think about that regimen again.

Now, might we say for the patients who have aBRCAmutation, maybe it’s better to think about PARP inhibitor versus VEGF inhibitor? I don’t think we know that for sure. I think people are trying to investigate further on GOG-213 and see whether there was any difference in response to those patients who hadBRCAstatus identified, but that translational science is still pending. As we look at sequencing, we think our patients almost always are going to have bevacizumab at some portion of their treatment. And whether that’s when they develop ascites or whether they need it up front, we still don’t know the answer. The drug has been around 15-plus years now, and we still don’t know the best place to use it and the best biomarker. So, when we look at biomarkers helping us, I think we can turn to the PARP inhibitors. And the homologous recombination defects are certainly a signal that probably helps us sequence those patients.

Choosing among the different PARP inhibitors is tricky. I think it’s hard to do cross-trial comparisons and really tell us which one wins. Certainly, olaparib, we have the most experience with, although we had a change from capsules to tablets, which definitely made the large pill burden better. It’s a fairly well tolerated PARP inhibitor. There are just some unique toxicities that sometimes help drive decisions that we make. The niraparib in patients with prior platelet toxicity maybe has a little bit more concern. Although, I think with appropriate dosing and monitoring, we can manage our patients with niraparib. Rucaparib has also some unique features in that we can see some elevations to the liver enzymes and this elevation in creatinine. Neither one really is a clinically meaningful problem, but it’s just something we have to monitor and be aware of. I think they all have their pluses and minuses, and it’s nice to have them all available to use for our patients. When we get to cost strategies, there are slight differences in costs, but I’m not sure that’s enough to drive things completely at this time.

Transcript edited for clarity.