Expanding Role of PARP Inhibitors in Advanced Ovarian Cancer - Episode 19
Michael Birrer, MD: The SOLO-1 data were the first data we had that showed that PARP [poly (ADP) ribose polymerase] inhibition for BRCA1 and BRCA2 patients as a maintenance therapy was quite effective after upfront therapy. This has not been lost by the other companies, and niraparib is being tested in the PRIMA study. The difference is the PRIMA study is a lot like the NOVA study, meaning that it is all-comers, not BRCA1 and BRCA2. So this would include HRD [homologous recombination deficiency] patients, and it would also include truly wild-type tumors. To be perfectly honest, I think all of us expect PRIMA to be positive. It’s will move niraparib up into first-line maintenance. And it will expand it to potentially expanded to include all patients. The parallel study for rucaparib is ATHENA, and that is also ongoing.
We think it is important to recognize beyond the movement of all parts into frontline therapy. Careful thought is being taken to rationally combine PARP inhibition with other agents. This is important for 2 reasons. First of all, there are other agents already in that area. So for instance some of our patients upfront will get bevacizumab. Which patients should get bevacizumab, which patients should get PARP? We’re having that debate. PARP is probably relegated right now to BRCA1 and BRCA2 patients. Bevacizumab could essentially be all others, or at least all others that we think are high risk. Ultimately, combining PARP and bevacizumab makes sense. And those studies are ongoing. And so in the fairly short period of time we may have an answer that the combination is most effective, and then we won’t have to essentially decide who should and should not get the combination.
PARP inhibitors are also being combined with immuno-oncology drugs. The idea here is that a tumor that has a DNA repair abnormality will have a lot of mutations. They’ll create neoantigens. Neoantigens will be recognized by the immune system so it’s a rational combination. There are essentially too many I/O P[immuno-oncology] ARP combinations for me to actually quote. But, but it’s important to recognize that those results will be coming out.
Ursula A. Matulonis, MD: Currently, there are no effective screening tools for patients for ovarian cancer at this point for our patients. Our patients typically present with either advanced disease and will present with symptoms of advanced disease, so abdominal distention or abdominal bloating; or patients with early stage cancer will present with pelvic discomfort and just happen to come to their physician’s attention. I think that a good place to start for screening would be to test different screening techniques for patients who already have an elevated risk of ovarian cancer.
So, for those patients who have an underlying germline BRCA1 and BRCA2mutation, if they are found to have this mutation when they’re 30 or in their 20s, when’s the optimal time to undergo risk-reducing surgeries? How do we detect early lesions? How do we help these women who we know have an elevated risk make that decision? Are they going to eventually develop this cancer? We don’t know that. For BRCA1, for example, it’s about a 40% risk that those patients eventually develop ovarian cancer. So not all women with underlying BRCA mutations will develop ovarian cancer.
So we need to help those women figure out if they are destined to develop ovarian cancer, yes or no, and then help younger women decide when should they have risk-reducing surgery. Because you don’t want to happen when they’re 20. You want it to happen when they’re in their 40s or 50s. But you want to make that decision based upon real data telling them when their highest risk of developing the cancer is really going to be.
Michael Birrer, MD: The parting comment I would make is the historic perspective. For 20 years we essentially talked about carboplatinum and Taxol. We had these side arguments about Taxol versus Taxotere, IP [interperitoneal] versus IV [intravenous]. They were in many ways academic exercises as opposed to helping our patients. That has completely changed with the approval of bevacizumab and antiangiogenic agents, the approval of the PARP inhibitors. We have meaningful choices for our patients, which is good for them. And the challenge for physicians is to personalize this approach to provide the greatest opportunity for patients to benefit with the least toxicity
Transcript Edited for Clarity