Dr. Naumann on Unanswered Questions With PARP Inhibitors in Ovarian Cancer

R. Wendel Naumann, MD, gynecologic oncologist, Levine Cancer Institute, Carolinas HealthCare System/Atrium Health, discusses unanswered questions with PARP inhibitors in ovarian cancer.

Patients with ovarian cancer should be tested for BRCA mutations, particularly now that 2 PARP inhibitors—–olaparib (Lynparza) and niraparib (Zejula)––are approved for use as frontline maintenance therapy, says Naumann. Though not yet approved, the combination of olaparib and bevacizumab (Avastin) has also shown a benefit as frontline maintenance therapy, according to data from the phase 3 PAOLA-1 trial. Now, the field has to determine whether to give maintenance therapy, and the type of therapy to administer, says Naumann. Historically, high-risk patients received bevacizumab, and now patients with BRCA mutations are being put on PARP inhibitors first.

In addition to determining whether to prescribe PARP inhibitors in all-comers, patients with homologous recombination deficiency, or only those with BRCA mutations, the field will have to determine how the use of PARP inhibitors as frontline maintenance therapy will impact treatment in the second- and third-line settings, reexposure to PARP inhibitors, and the optimal timing of bevacizumab.

In doing so, the risks and benefits of therapy should be considered, says Naumann. Recurrence should also factor into the decision. For example, if bevacizumab can only be used 1 time, is it more prudent to give it up front, or is it more prudent to wait and hold it for recurrence? Those questions will need to be answered in the coming years, concludes Naumann.