Impact of Cyclin-Dependent Kinase 4 and 6 Inhibitors on Chemotherapy Utilization and Overall Survival in Women with HR+/HER2– Metastatic Breast Cancer in the United States

Purpose: Delaying chemotherapy remains a vital goal in therapeutic management of HR+/HER2– metastatic breast cancer (MBC). However, recent reports continue to highlight substantially high chemotherapy utilization in earlier therapy lines. In this study, we explored the impact of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy class, introduced in 2015, on early chemotherapy utilization in an older population of patients with HR+/HER2– MBC in the United States (US). Methods: Using an interrupted time series design, patients with a confirmed diagnosis of MBC aged ≥ 65 years initiating systemic therapy during 2010-2019 were selected from the SEER- Medicare database. The proportion of chemotherapy use was summarized quarterly based on the date of treatment initiation separately in the first, second, and third lines. Segmented regression models, adjusted for autocorrelation over time, were fitted to estimate trends before and after the availability of CDK4/6 inhibitors in the first quarter of 2015. Results: Of the 3,244 eligible women (median age at diagnosis: 74 years), all initiated first-line therapy; 47.9% (n=1,581) initiated second-line therapy, and 50.1% (n=792) initiated third-line therapy. Chemotherapy utilization in the period immediately after introduction of CDK4/6 inhibitor therapy decline by estimated 2.5% in the first line (P=0.408), 15.5% in the second line (P=0.005), and 16.3% in the third line (P=0.003). Conclusions: This population-based study illustrates that chemotherapy utilization in earlier therapy lines for HR+/HER2– MBC declined steadily between 2010 and 2019. These declines were significantly accelerated by the introduction of CDK4/6 therapy class in 2015, notably in the second- and third-line settings.