Cyclin-dependent kinase (CDK)4/6 inhibitors combined with endocrine therapy (ET) are the standard of care for first-line (1L) hormone receptor (HR)-positive/HER2-negative metastatic breast cancer. Although real-world studies have evaluated the comparative effectiveness of CDK4/6 inhibitors plus ET, many have been limited by small sample sizes and short follow-up durations. This study aimed to describe patient characteristics and treatment patterns for palbociclib (PAL), ribociclib (RIB), or abemaciclib (ABE) combined with an aromatase inhibitor (AI) in US routine clinical practice, leveraging a large dataset with extended follow-up.
This retrospective observational cohort study (NCT06495164) utilized the US Flatiron Health Research Database, which includes data from more than 750,000 patients with breast cancer. Adult HR-positive/HER2-negative metastatic breast cancer patients who initiated treatment with 1L PAL, RIB, or ABE plus an AI between February 3, 2015 and July 31, 2024, were included. Patients were followed from the start of CDK4/6 inhibitors plus AI treatment until January 31, 2025, death, or last medical activity. Treatment duration was defined as the time from the start to the end of the index therapy or death. Descriptive analyses were used to evaluate baseline demographics and clinical characteristics. The Kaplan-Meier method with Cox regression models and stabilized inverse probability of treatment weighting (sIPTW, primary analysis) were used to assess treatment patterns and outcomes.
Among 11,557 eligible patients, 8109 received PAL plus AI, 2006 received RIB plus an AI, and 1442 received ABE plus AI. Patients in the PAL group were 2 to 3 years older than those in the RIB and ABE groups, whereas premenopausal patients were more prevalent in the RIB group. After sIPTW, baseline demographics and clinical characteristics were fairly balanced across CDK4/6 inhibitor groups. Median follow-up durations were 32.1 months for PAL, 16.7 months for RIB, and 20.1 months for ABE. Median treatment duration was 20.7 months for PAL, 18.3 months for RIB (adjusted hazard ratio vs PAL, 1.12; 95% confidence interval [CI]: 1.05-1.20; P=.0008), and 17.1 months for ABE (adjusted hazard ratio vs PAL, 1.13; 95% CI: 1.05-1.22; P=.0012). Discontinuation rates at 12 months were 33.3% for PAL, 39.4% for RIB, and 41.1% for ABE.
Subsequent treatments were received by 49.9% of patients in the PAL group, 37.3% in the RIB group, and 39.4% in the ABE group. CDK4/6 inhibitor−based regimens accounted for 42.3%, 54.1%, and 55.7% of subsequent therapies for the PAL, RIB, and ABE groups, respectively, whereas ET alone and chemotherapy alone were less frequently used. Of those treated with 1L PAL and who received subsequent treatment, 5.2% of patients switched to RIB and 10.1% switched to ABE with or without changing their AI partner. CDK4/6 inhibitor switching rates were higher in the RIB group (20.3% switched to PAL; 14.1 switched to ABE) and ABE group (23.1 switched to PAL; 7.8% switched to RIB).
This large real-world study highlights differences in patient characteristics, treatment duration, and subsequent therapies across 1L CDK4/6 inhibitors in HR-positive/HER2-negative metastatic breast cancer. PAL demonstrated longer treatment duration compared with RIB and ABE. Patients who started 1L RIB and ABE were more likely to switch CDK4/6 inhibitors, most often to PAL. Further research is needed to explore the clinical outcomes associated with subsequent treatment strategies and to identify factors influencing treatment choice and duration in routine practice.
Source: Brufsky AM, Layman RM, Liu X, et al. Treatment duration and subsequent treatments of first-line (1L) CDK4/6i plus aromatase inhibitor (AI) for HR-positive/HER2-negative metastatic breast cancer (MBC) in US routine clinical practice. Presented at: ESMO Congress 2025. October 20, 2025; Berlin, Germany. Abstract 523P.