Dr Crane on PARP Inhibitor Maintenance in Ovarian Cancer

Erin K. Crane, MD, MPH, associate professor, Division of Gynecologic Oncology, Atrium Health Levine Cancer Institute, discusses findings from 3 trials demonstrating the benefits of PARP inhibitor maintenance in patients with ovarian cancer.

The phase 3 SOLO1 trial (NCT01844986) randomized patients with somatic or germline BRCA-mutated ovarian cancer who had completed chemotherapy to receive either olaparib (Lynparza) or placebo. Long-term findings from this trial continue to display the practice-changing benefits of olaparib in the BRCA-mutant population, Crane says. The 7-year overall survival rate in the olaparib arm was 67.0% vs 46.5% in the placebo arm.

The phase 3 PRIMA trial (NCT02655016) enrolled all-comers with ovarian cancer who had received frontline platinum-based chemotherapy, including those with BRCA mutations, those with homologous recombination deficiency (HRD)–positive ovarian cancer, and those with homologous recombination–proficient tumors. These patients were randomly assigned 2:1 to receive niraparib (Zejula) or placebo. Data from the primary analysis of this trial showed that in all-comers, the median progression-free survival (PFS) was 13.8 months vs 8.2 months with niraparib and placebo, respectively. In the HRD-positive population, the median PFS was 21.9 months with niraparib vs 10.4 months with placebo. These findings led to the 2020 FDA approval of niraparib maintenance in adult patients with ovarian cancer who responded to frontline platinum-based chemotherapy, regardless of BRCAmutation or HRD status.

The phase 3 PAOLA-1 trial (NCT02477644) randomized patients with ovarian cancer to receive olaparib plus bevacizumab (Avastin) or bevacizumab alone as frontline maintenance therapy after completing chemotherapy, regardless of BRCA mutation or HRD status. Treatment with the combination resulted in a median PFS of 22.1 months vs 16.6 months in those who received bevacizumab alone. The combination provided a notable benefit in patients with HRD-positive disease, including those with BRCA mutations, with a median PFS of 37.2 months vs 17.7 months in the bevacizumab-alone arm. These findings supported the 2020 FDA approval of olaparib plus bevacizumab in the frontline maintenance setting in patients with HRD-positive ovarian cancer.

As these 3 study populations differed slightly from one another, the indications for these 3 PARP maintenance regimens differ as well, Crane concludes.