Can PARP Inhibitor Eligibility Be Expanded in Ovarian Cancer?

In patients with ovarian cancer, somatic and germline mutations in non-BRCA1 and BRCA2 homologous recombination deficiency (HRD) genes are rare, detected in less than 5% of tumors. Although interest in utilizing poly (ADP-ribose) polymerase (PARP) inhibitors for the treatment of recurrent ovarian cancer beyond BRCA1 and BRCA2 carriers has been growing, new data show that only a small percentage of patients with ovarian cancer might benefit from these drugs, according to research presented by Julia Fehniger, MD, from NYU Langone Health, at the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer.

Dr Fehniger and colleagues sought to characterize the prevalence of somatic and germline mutations in non-BRCA1 and BRCA2 HRD pathway genes among patients with ovarian cancer. They reviewed comprehensive genomic profiling (CGP) of tumor tissue for all patients from a single institution (Foundation Medicine, Cambridge, MA) between January 2014 and July 2019. They also collected germline genetic testing results from patients with newly diagnosed ovarian cancer who participated in a prospective research study of germline genetic testing from October 2015 to October 2018.

Alterations in non-BRCA1 and BRCA2 HRD genes, including ATM, BARD1, BRIP1, PALB2, RAD51C, and RAD51D, were included, and clinicopathologic and treatment data were extracted from the electronic medical record.

In this study, a total of 79 patients underwent tumor CGP, and 133 patients underwent germline genetic testing. Among those whose tumors underwent CGP, 3 (4%) had somatic mutations in non-BRCA1 and BRCA2 HRD genes. In the patients who had germline genetic testing, no non-BRCA1 or BRCA2 HRD mutations were found.

One patient each had an ATM, BRIP1, and RAD51C mutation on tumor CGP. All patients with mutations on tumor testing underwent panel germline genetic testing, and no pathogenic mutations were identified. All patients with non-BRCA1 and BRCA2 HRD mutations had stage III disease, with initial disease-free intervals of 18 to 23 months after primary therapy, the investigators reported.

“Although PARP inhibitors may benefit this patient population, our data suggest they represent a small percentage of ovarian cancer patients,” the researchers concluded. “Further study confirming these data in a larger cohort of ovarian cancer patients, as well as testing the efficacy of PARP inhibitors in these patients, is needed.”


  • SGO 2020 Annual Meeting on Women’s Cancer. Abstract 218.

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