A Real-World Evidence Study of CDK4/6 Inhibitor Treatment Patterns and Outcomes in Metastatic Breast Cancer by Germline BRCA Mutation Status

Introduction Limited data exist on real-world treatment patterns and the effectiveness of cyclin-dependent kinase (CDK) 4/6 inhibitors in germline BRCA (g BRCA )-mutated breast cancer. Methods Adults with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (mBC) treated with CDK4/6 inhibitor therapy between 2013 and 2018 were retrospectively selected from the Flatiron Health database. Patients with known g BRCA status were classified as mutated (g BRCA m) or wild type (g BRCA wt). Time-to-first subsequent therapy or death (TFST) and overall survival (OS) were calculated from the earliest line of therapy with a CDK4/6 inhibitor. Results Of 2968 patients with HR+/HER2− mBC receiving a CDK4/6 inhibitor, 859 (28.9%) had known g BRCA status, of whom 9.9% were g BRCA m and 90.1% g BRCA wt. Median (95% confidence interval [CI]) TFST was 10 (7–11) months in the g BRCA m group, 10 (9–11) months in the g BRCA wt group, and 11 (10–12) months in the combined g BRCA wt and unknown g BRCA group; median (95% CI) OS was 26 (21–not estimated), 37 (31–51), and 33 (31–35) months, respectively. Cox models indicated the g BRCA m group had shorter TFST (stratified hazard ratio [sHR] 1.24; 95% CI 0.96–1.59) and OS (sHR 1.50; 95% CI 1.06–2.14) than the g BRCA wt group. The g BRCA m group had shorter TFST (sHR 1.38; 95% CI 1.08–1.75) and OS (sHR 1.22; 95% CI 0.88–1.71) than the combined group. Conclusion The results of this real-world study suggest that treatment outcomes with CDK4/6 inhibitors may be worse in patients with g BRCA m mBC than in their counterparts with g BRCA wt and unknown g BRCA status, suggesting potential differences in tumor biology. This result highlights the unmet need in patients with g BRCA m requiring optimized treatment selection and sequencing. Future exploration in larger samples of patients who have had biomarker testing is warranted.