Advanced Ovarian Cancer: New Perspectives on Systemic Therapy - Episode 8

PARP Inhibitors and Indications in Ovarian Cancer


Bradley J. Monk, MD, FACS, FACOG: One of my messages is that all PARP inhibitors are not the same. They have different doses and different frequencies. Niraparib is once daily. The others are twice daily. They have different lipophilicity, different tissue distribution, and different metabolism. They have the idiosyncratic, adrenergic complication. We’re into this for 5 years. The first PARP inhibitor was approved in ovarian cancer in December 2014, so we’re way down this life cycle. These are different agents. What is probably the most important is the indication. Why do doctors do what they do? They do so based on an indication, because that informs reimbursement, and an indication is related to a clinical trial. Michael, my question for you—we’ve talked about veliparib and niraparib. Do you think there’s just going to be an opportunity to say, “I’m going to use rucaparib or olaparib in HRD-positive patients in frontline maintenance”? Or do you think payers, providers, and the NCCN [National Comprehensive Cancer Network] are going to hold us to these clinical trials? You know that olaparib or rucaparib is going to work in an HRD [homologous recombination deficient] patient in frontline maintenance.

Michael J. Birrer, MD, PhD: Yes.

Bradley J. Monk, MD, FACS, FACOG: Does it really matter what you know?

Michael J. Birrer, MD, PhD: It’s interesting, because I would add that to what you said before, which is that they’re different agents. I think from the efficacy standpoint, particularly in the BRCA patients, they’re very equivalent. When I was in Massachusetts, it was different. Now I’m in Alabama. Third-party reimbursement is pretty specific. I don’t think you’re going to be able to substitute rucaparib, for instance—which does have a trial that supports it—willy-nilly to use it. On the other hand, and I’ll throw back to Rob to be controversial: Based on those results in VELIA, do you actually think that AbbVie Inc will go forward with the registration? The reason I ask that is because they’re late to the party. There are going to be a lot of drugs in that space. Niraparib will probably beat them, and olaparib is already there. You’ve got some increase in toxicity. Maybe the hazard ratios aren’t quite as good, and we know the concurrent treatment isn’t effective. It’s a maintenance strategy, and there’s a lot of marketing for that. What do you think?

Robert L. Coleman, MD, FACOG, FACS: I like that. Thanks for the question. I think it really gets back to what you’re going to do when you’re in the clinic next week. Shannon just brought this up. You have a patient you just operated on and you have the options of nothing in addition to chemotherapy, BEV [bevacizumab] in addition to chemotherapy, or—if it’s approved for us and we can use it—a PARP inhibitor in combination with chemotherapy. You can make that touch point right then. We talked about how strong the effect can be in patients who are BRCA-positive, either tumor or germline. Although we included the HRD, even if we didn’t have that information, we still have evidence from the whole trial population that we can use a PARP inhibitor in there. Your first decision is going to be, how does it fit with that? Are you going to use something then or not?

That’s going to be the first thing. For me, I do think if I had it available and I had a BRCA-positive or HRD-positive patient whom I knew the data for, I’d be comfortable giving it then, because I know I’m going to have that efficacy that’s supported by the trial. I wouldn’t prospectively withhold it to get to the maintenance phase just so I could use 1 of these others if I already knew I was going to want to use a PARP inhibitor right up front. Do you see what I’m saying?

Transcript Edited for Clarity