Real-World Germline BRCA Testing, Poly(ADP-ribose) Polymerase Inhibitor Utilization, and Survival Outcomes in Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer.

Abstract

Testing for germline <i>BRCA1</i> and/or <i>BRCA2</i> mutations (gBRCAm) is recommended for patients with human epidermal growth factor receptor 2-negative (HER2-) breast cancer (BC) to guide treatment selection with poly (ADP-ribose) polymerase inhibitors (PARPis). However, real-world data on germline <i>BRCA1</i> and/or <i>BRCA2</i> (gBRCA) testing and PARPi treatment patterns in metastatic BC (mBC) are limited. Deidentified patient data from adults diagnosed with HER2- mBC between 2014 and 2022 were captured from electronic health records in the US Flatiron Health database. gBRCA testing patterns and prevalence were examined by tumor subtype (hormone receptor-positive [HR+]/triple-negative) and disease stage at diagnosis. Demographic and clinical characteristics were described by receipt of gBRCA testing and PARPi. PARPi treatment patterns were assessed, and real-word overall survival (OS) was estimated in patients with gBRCAm diagnosed with mBC after January 1, 2018. Of the 15,006 total patients, 4,654 (31.0%) received a gBRCA test. gBRCA testing rates mostly increased from 2014 to 2022 and were lower in patients with HR+ than triple-negative tumors. Of the patients who underwent gBRCA testing, 337 (7.2%) had gBRCAm. From 2018 to 2022, PARPi was initiated in 94 (45.6%) of 206 patients with gBRCAm. With a median follow-up of 22.8 months across patients with available first-line treatment start dates, real-world OS was numerically longer among 94 patients with gBRCAm who received PARPi (32.3 months [95% CI, 22.7 to 47.4]) than among 99 patients who did not (21.9 months [95% CI, 18.4 to not reached]). Although gBRCA testing increased over time, testing and PARPi utilization rates remained suboptimal in potentially eligible patients with HER2- mBC. Exploratory analysis showed numerically longer OS in patients who received PARPi. Wider and timelier gBRCA testing is warranted to inform potentially optimal treatment decisions.