Ovarian Cancer: Molecular Testing and PARP Inhibitors

Matthew A. Powell, MD:So, the question about molecular testing for ovarian cancers, primary peritoneal cancers, and fallopian tube cancers has recently changed, with the NCCN guidelines now suggesting that we should test our patients not only for germline mutations but also at the time of recurrence—consider testing those patients’ tumors somatically. We actually evaluate the tumor for microsatellite instability to see whether they’re a candidate for immunotherapy, also suggesting that we test forBRCA1andBRCA2genes and homologous recombination. This may help inform us about sequencing of adjuvant therapies and maintenance strategies.

Selecting for patients who should be tested for germline mutations is really easy. All our patients with epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer should be tested or at least offered testing, not only to help inform us about their family and cascade testing for their family but also perhaps for selecting therapies. Selecting patients for somatic testing of their tumor—right now we recommend that at time of first recurrence.

Predicting response to platinum therapy is tricky. We can use a few things, like how they did with their prior platinum is a very good response. The platinum-free interval can help us predict how they’re going to do with platinum when we use it for second- or third-line therapy. But we know that other molecular features, likeBRCAgene status and homologous recombination defect, probably also help us predict for platinum sensitivity.

This is a very exciting time for our patients with ovarian cancer in that we have a lot of new therapies, and one of the biggest categories is PARP inhibitors. We have 3 new PARP inhibitors—I say new; some of them have been out a few years—to choose from: olaparib, rucaparib, and niraparib. They all have now a maintenance indication, so we can use them after 2 prior platinum chemotherapies in a complete response to a partial response, to be used as a maintenance strategy. Also, 2 of the medications have a treatment indication, with rucaparib and olaparib having also a treatment indication after 3 lines of prior therapy.

Transcript edited for clarity.