Dr. O'Malley on Maintenance Rucaparib in Non-BRCA HRR-Mutated Ovarian Cancer

David O’Malley, MD, professor in the Department of Obstetrics and Gynecology at The Ohio State University College of Medicine, and director of the Division of Gynecologic Oncology at The Ohio State University Comprehensive Cancer Center—The James, discusses the rationale to evaluate the clinical benefit of rucaparib (Rubraca) maintenance treatment following disease progression in a subgroup of patients with ovarian cancer whose disease is associated with a mutation in a non-BRCA homologous recombination (HRR) gene in the phase III ARIEL3 trial in ovarian cancer.

ARIEL3 was a randomized, double-blind, placebo-controlled, phase III trial that enrolled patients with platinum-sensitive ovarian cancer, says O’Malley. Patients were randomized 2:1 to receive either rucaparib or placebo. Rucaparib maintenance treatment was found to significantly improve progression-free survival in all predefined, nested cohorts, including BRCA-mutant, BRCA-mutant plus BRCA wild-type/high loss of heterozygosity, and the intent-to-treat population.

In the patient population, prespecified non-BRCA HRR genes were detected, as well; these prespecified non-BRCA HRR genes were also evaluated in the ARIEL2 trial, says O’Malley. In addition to BRCA, RAD51C/D, BRIP1, and PALB2 are significantly associated with hereditary ovarian cancer, adds O’Malley. Investigators have also found that PALB2 and RAD51C/D are casually associated with clinical sensitivity with PARP inhibitors.

The goal of the research released at the 2020 SGO Annual Meeting was to analyze post-progression outcomes in order to evaluate the continued benefit of rucaparib maintenance therapy in this subgroup of patient with non-BRCA HRR genes, concludes O’Malley.