Background: Limited data exist on the real-world treatment patterns and effectiveness of cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors in the germline BRCA (gBRCA) mutated breast cancer population. Methods: Adults with human epidermal growth factor receptor 2 negative (HER2-), hormone receptor positive (HR+) metastatic breast cancer (mBC) treated with a CDK4/6 inhibitor from 01Jan2013–31Jan2018 were retrospectively selected from the Flatiron Health Oncology electronic medical record database. Patients with known gBRCA status were classified as having gBRCA mutated (gBRCAm) or wild type (gBRCAwt) disease. Time to first subsequent therapy or death (TFST) and overall survival (OS) were calculated from start of the earliest line of therapy with a CDK4/6 inhibitor. Kaplan-Meier (KM) medians were estimated, and TFST and OS compared between gBRCA groups with Cox models stratified by line of therapy and adjusting for demographic and clinical characteristics that modified hazard ratios (HRs) for gBRCA status by > 10%. Results: Of 2968 HER2- HR+ patients with mBC receiving a CDK4/6 inhibitor, gBRCA status was known for 859 (28.9%). Patients with gBRCAm and gBRCAwt received letrozole plus palbociclib (42.4 and 39.8%, respectively), fulvestrant plus palbociclib (32.9 and 30.7%), or other CDK4/6 regimens (24.7 and 29.5%) across all lines. The gBRCAm group had a non-significant, shorter TFST than gBRCAwt (stratified HR 1.24; 95% CI 0.96–1.59). OS was significantly shorter in gBRCAm than gBRCAwt patients (stratified HR 1.50; 95% CI 1.06–2.14). Conclusions: The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be poorer in patients with gBRCAm compared with gBRCAwt disease. These findings indicate a higher unmet need among patients with gBRCAm, potentially requiring alternative treatment options.

*Data are KM median (95% confidence interval [CI])