HRR Mutation Status Prognostic of Survival Outcomes for Women with Relapsed Platinum-Responsive Ovarian Cancer

Results of a biomarker analysis from the NRG Oncology NRG-GY004 trial were presented in a seminal session at the Society for Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer in March 2022. The analysis, which took place as part of a pre-planned translational endpoint for the study, concluded that homologous recombination repair mutant type (HRRmt) was prognostic for progression-free survival and predictive of olaparib activity compared to standard of care, platinum-based chemotherapy for women with relapsed platinum-responsive ovarian cancer.

The NRG-GY004 trial did not achieve its primary objective of improving progression-free survival in this patient population by treating with olaparib alone or a combination of olaparib and cediranib compared to usual chemotherapy. However, data collected from the trial suggested that study participants with BRCA mutations displayed clinically significant activity in a predefined assay when treated with the investigational drugs.

The status of homologous recombination deficiency (HRD) was successfully measured by the BROCA-HR test for 470 of the 565 patients included in the trial. BROCA-HR is a next-generation targeted sequencing platform including all known gynecological cancer susceptibility genes and other DNA repair or related genes, as well as a 3100 single nucleotide polymorphism panel for the loss of heterozygosity (LOH) analysis. The genes included as HRD were ATM, BARD1, BRCA1, BRCA2, NBN, PALB2, RAD51C and RAD51D. BRCA1 and BRCA2 mutations accounted for 90% of HRR mutations in the analysis.

“This analysis let us know that a subset of the population of women treated in the trial experienced significant clinical benefit from olaparib or the combination of olaparib and cediranib,” Joyce said. F. Liu, MD, MPH of the Dana-Farber Cancer Institute and study chair for the NRG-GY004 trial. “Due to the potential complications of repeated exposure to platinum-based chemotherapy in women with relapsed platinum-sensitive ovarian cancer, it is critically important to continue testing less burdensome treatment alternatives for the patient with the same efficacy. More personalized and targeted approaches could benefit some patients depending on the biomarker subset.”

Although LOH status was also explored, LOH was not prognostic for progression-free survival independent of BRCA status. LOH was also not predictive of the activity of either experimental treatment arm compared to chemotherapy.

Provided by NRG Oncology