Ovarian Cancer: Selecting an Appropriate PARP Inhibitor
Insights From: Oliver Dorigo, MD, PhD, Stanford University Medical Center; Whitney Graybill, MD, MS, Medical University of South Carolina; Matthew Powell, MD, Washington University School of Medicine
Matthew Powell, MD: How do I choose among the 3 different PARP inhibitors? Obviously, rucaparib has its unique indication for somatic and germline mutations in patients with measurable disease who are not in the maintenance setting. That drug has its unique indication there. So, if you have a somatic BRCA mutation, that’s really the only drug you could use in a treatment-type phase at this point. We could use olaparib in a germline BRCA population after 3 prior lines of therapy, and then we have the maintenance indications that are similar between niraparib and olaparib. After 2 prior platinum compounds in a CR or PR, those drugs can be used.
As far as choosing which drug to use, there may be some hint as to how they did on their most recent platinum drug or what their most recent therapies showed. If they had a lot of platelet problems, we may choose to not use niraparib, although I don’t have any good data about that. We’re just a little more nervous about some of the platelet toxicity of niraparib in patients who had a lot of thrombocytopenia, so I might choose olaparib in that population.
For the patients who have a lot of baseline nausea, it may drive the single-day dosing strategy of niraparib, where those patients can take 1 dose right before bed, and perhaps they don’t suffer quite as much nausea. For patients with hypertension, you may make a choice away from niraparib, as we do know that it can worsen hypertension. But outside of that, the differences are mostly in style and maybe not as much in substance. Perhaps the dose intensification with niraparib may make a difference, especially in that nongermline-BRCA, non-HRD population where that extra dose intensification may be making a difference.
Whitney S. Graybill, MD, MS: In the maintenance setting, when I’m evaluating a patient for a PARP inhibitor, the 2 drugs that are currently FDA approved in this setting would be niraparib and olaparib. One thing that I take into consideration is dosing. Niraparib is once-a-day and olaparib is twice-a-day dosing, and I also look at the side effect profile for both drugs.
In the treatment setting, it varies depending on whether a patient has a germline BRCA mutation or whether it’s somatic. If they have a germline BRCA mutation, they’re eligible for either rucaparib or olaparib, but if they have only a somatic mutation, then that makes them eligible for rucaparib. And again, I look at adverse effect profiles, quality of life, and what the patient wants.
In terms of the data that we have from the PARP inhibitor trials, it appears that patients respond better to a PARP inhibitor in the setting of platinum-sensitive disease, a germline or somatic BRCA mutation. I think it makes sense to try to put patients on PARP inhibitors earlier, before they become platinum resistant. That’s why I tend to currently use them in the maintenance setting.
Oliver Dorigo, MD, PhD: Olaparib and niraparib are approved for the maintenance setting, and I choose between those 2 drugs if I have a patient who has platinum-sensitive recurrent disease. Niraparib does cause a fair degree of thrombocytopenia. If I have a patient who is severely bone-marrow suppressed and cannot recover from the severe bone-marrow suppression in a timely fashion—within 8 weeks as recommended by the FDA—I might choose olaparib.
Niraparib, otherwise, is a drug that was studied in a patient population that included not only BRCA1 and BRCA2 mutation carriers but all-comers. And the NOVA trial clearly shows a benefit for all patients, regardless of HRD status and regardless of BRCA1 and BRCA2 mutations. I tend to choose niraparib if I see that the patient will tolerate this drug. Rucaparib and olaparib are both approved for the treatment of a patient with ovarian cancer with recurrent disease. If patients have BRCA1 and BRCA2 mutations, I strongly consider either one of them. If there is no germline mutation and I see a somatic mutation in the tumor, then rucaparib is my drug of choice, and it’s approved for this indication.