HRR Mutational Status May Be Prognostic of Survival Outcomes for Women With Recurrent Platinum-Sensitive Ovarian Cancer
Results of a biomarker analysis of the NRG Oncology NRG-GY004 trial were presented during the Society for Gynecologic Oncology’s (SGO) Annual Meeting on Women’s Cancer. The analysis, which occurred as part of a preplanned translational endpoint for the study, concluded that homologous recombination repair (HRR) mutation type was prognostic of progression-free survival and predictive for activity of olaparib when compared to the standard of care—platinum-based chemotherapy—for women with recurrent platinum-sensitive ovarian cancer.
The NRG-GY004 trial did not reach its primary goal of improving progression-free survival in this patient population by treatment with either olaparib alone or a combination of olaparib and cediranib when compared to the usual chemotherapy. However, data collected on the trial suggested that study participants with BRCA mutations displayed clinically significant activity in a prespecified analysis when treated with the experimental drugs.
Homologous recombination deficiency (HRD) status was successfully measured by the BROCA-HR assay for 470 of the 565 patients enrolled on the trial. BROCA-HR is a targeted next generation-sequencing platform including all known gynecologic cancer susceptibility genes and other DNA-repair or related genes, as well as a 3,100 single-nucleotide polymorphism panel for loss of heterozygosity (LOH) analysis. Genes included as HRD were ATM, BARD1, BRCA1, BRCA2, NBN, PALB2, RAD51C, and RAD51D. BRCA1 and BRCA2 mutations comprised of 90% of the HRR mutations in the analysis.
Joyce F. Liu, MD, MPH
“This analysis provided us with the knowledge that a subgroup of the population of women treated on the trial derived significant clinical benefit from olaparib or combination olaparib and cediranib,” stated Joyce F. Liu, MD, MPH, of the Dana-Farber Cancer Institute, and the study chair of the NRG-GY004 trial. “Due to the potential complications from repeated exposure to platinum-based chemotherapy experienced by women with recurrent platinum-sensitive ovarian cancer, it is incredibly important to continue to test treatment alternatives that incur less of a burden on the patient with the same efficacy. More personalized, targeted approaches could benefit certain patients depending on the biomarker subgroup.”
Although LOH status was also explored, LOH was not prognostic for progression-free survival independent of BRCA status. LOH was also not predictive for activity of either experimental treatment arm when compared to chemotherapy.
Disclosure: This study was supported by National Cancer Institute grants to NRG Oncology SDMC (1U10 CA180822), NRG Operations (U10CA180868), and U24CA180803 (IROC). Additionally, Canadian Cancer Trials Group (CCTG) participation in this trial is supported through its grant from the U.S. National Cancer Institute (NCI) of the National Institutes of Health under the award CA180863. Additional programmatic funding support for the CCTG is provided by the Canadian Cancer Society (#704970) and the Canada Foundation for Innovation. The NCI’s National Clinical Trials Network participated in the study. Funding and support was also received from AstraZeneca through a Cooperative Research and Development Agreement with NCI.The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.