106 Treatment Durations, Subsequent Treatments, and Switching of First-Line Cyclin-Dependent Kinase 4/6 Inhibitors in Patients with HR+/HER2− Metastatic Breast Cancer in US Routine Clinical Practice

Background

CDK4/6 inhibitors (CDK4/6i) plus endocrine therapy are the first-line standard of care for hormone receptor–positive/HER2-negative (HER2–negative) metastatic breast cancer. A growing body of real-world studies (RWS) has reported the comparative effectiveness of CDK4/6i plus endocrine therapy, but most have small sample sizes and/or short follow-up. This large RWS evaluated treatment durations and subsequent treatments of patients with hormone receptor–positive/HER2− treated with palbociclib, ribociclib, or abemaciclib plus an aromatase inhibitor (AI) in US routine clinical practice.

Methods

Adult patients with HR+/HER2− metastatic breast cancer who started first-line palbociclib, ribociclib, or abemaciclib plus an aromatase inhibitor (February 2015−July 2024) were selected from the US-based Flatiron Health Research database. Patients were followed to January 31, 2025, death, or last medical activity. CDK4/6i treatment duration was defined as the time from the start of the specific CDK4/6i to treatment discontinuation or death. Stabilized inverse probability of treatment weighting (sIPTW) was performed. Kaplan−Meier analyses estimated treatment durations.

Results

Of 11,557 eligible patients, 8109, 2006, and 1442 received palbociclib plus an aromatase inhibitor, ribociclib plus an aromatase inhibitor, and abemaciclib plus an aromatase inhibitor, respectively. Median age of patients in the palbociclib group was 2 to 3 years older than abemaciclib and ribociclib groups. Premenopausal patients were more prevalent in the ribociclib group. Median follow-up durations were 32.1, 16.7, and 20.1 months in palbociclib, ribociclib, or abemaciclib groups. After sIPTW, treatment duration was longer for the palbociclib group than ribociclib and abemaciclib groups (median: 20.7 vs 18.3 vs 17.1 months, respectively; ribociclib vs palbociclib HR, 1.12 95% CI, 1.05-1.20], P = .0008; abemaciclib vs palbociclib HR, 1.13; 95% CI, 1.05-1.22] P = .0012). Ribociclib and abemaciclib groups had similar treatment durations (HR, 1.01; 95% CI, 0.92-1.11; P = .8280). Twelve-month treatment discontinuation rates were higher in ribociclib (39.4%) and abemaciclib (41.1%) groups than in the palbociclib group (33.3%). In the analysis of patients who initiated palbociclib. Ribociclib, or abemaciclib from 2017 onward when the three CDK4/6is were all approved in the US, 49.9%, 37.3%, and 39.4%, respectively, received subsequent treatments; CDK4/6i-containing regimens accounted for 42.3%, 54.1%, and 55.7%, respectively. CDK4/6i switching rates were higher in ribociclib (34.4%) or abemaciclib (30.9%) groups than in the palbociclib group (15.3%).

Conclusions

In this large RWS, patients with hormone receptor–positive/HER2− metastatic breast cancer who initiated first-line palbociclib had prolonged treatment duration and lower discontinuation rates than those who initiated first-line ribociclib or abemaciclib. Patients who started first-line ribociclib or abemaciclib were more likely to switch CDK4/6i, most often to palbociclib. Further research is needed to understand clinical outcomes associated with subsequent therapies.

Funding source: This work was supported by Pfizer Inc, USA.

Acknowledgment: Medical editorial support, conducted in accordance with Good Publication Practice (GPP3) and the International Committee of Medical Journal Editors (ICMJE) guidelines, was provided by Melissa Lingohr-Smith, PhD, of Oxford PharmaGenesis, Inc., Wilmington, DE, USA with funding provided by Pfizer Inc, USA.