Dr Goldsberry on PARP Inhibitor Selection in Advanced Ovarian Cancer

“I'm hesitant to put patients on any type of PARP inhibitor unless they are homologous repair–deficient or [harbor] a BRCA mutation. If they do [have one of these markers], then, right now, I'm thinking olaparib is probably the best choice [among approved PARP inhibitors], given the overall survival data from [phase 3] SOLO 1 trial that's out compared with the phase 3 PRIMA trial data [for niraparib].”

Whitney Goldsberry, MD, assistant professor, Department of Obstetrics, Gynecology and Women's Health, University of Louisville School of Medicine, discusses key considerations for selecting a PARP inhibitor in the maintenance treatment of patients with ovarian cancer, noting the importance of biomarker status in guiding therapy decisions.

PARP inhibitors, including niraparib (Zejula) and olaparib (Lynparza), are approved by the FDA in the maintenance setting for patients with advanced ovarian cancer. Both agents are approved for the maintenance treatment of adult patients with deleterious or suspecteddeleterious germline or somatic advanced epithelial ovarian, fallopian tube or primary peritoneal cancer who are in complete or partial response to first-line platinum-based chemotherapy; however, olaparib is indicated only for patients harboring BRCA mutations, and niraparib is indicated for patients in this setting irrespective of biomarker status.

Although niraparib could be utilized in the all-comer population, Goldsberry highlights that there was a smaller progression-free survival (PFS) benefit observed in the homologous recombination–proficient (HRP) subset of patients during the phase 3 PRIMA trial (NCT02655016). Consequentially, Goldsberry expresses hesitancy in prescribing PARP inhibitors for this subgroup, given the modest benefit relative to potential toxicities.

For patients with homologous repair–proficient tumors or BRCA mutations, olaparib has emerged as her preferred choice, Goldsberry says. The phase 3 SOLO1 trial (NCT01844986) demonstrated significant overall survival (OS) benefits with olaparib vs placebo in patients with BRCA-mutated advanced ovarian cancer.

When selecting a PARP inhibitor, clinicians must balance efficacy with toxicity profiles. Both olaparib and niraparib are associated with class-specific adverse effects such as anemia, thrombocytopenia, and nausea, and individual patient tolerance and prior treatment history may influence decision-making, Goldsberry concludes.