Real-world treatment durations, subsequent treatments, and switching of CDK4/6 inhibitors among patients with HR+/HER2− metastatic breast cancer

Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6is), palbociclib, ribociclib, and abemaciclib, are approved for HR+/HER2- metastatic breast cancer (mBC). This real-world study evaluated treatment durations and subsequent treatments of patients with HR+/HER2- mBC who received CDK4/6is plus aromatase inhibitor (AI) in the US. Methods: Adult patients with HR+/HER2- mBC who initiated first-line (1 L) CDK4/6is plus AI (February 2015-July 2024) were selected from the US-based Flatiron Health Research database. Stabilized inverse probability of treatment weighting (sIPTW) was conducted. Kaplan-Meier analyses estimated treatment durations. Results: Of 11,557 patients, 8109, 2006, and 1442 received 1 L palbociclib, ribociclib, and abemaciclib, respectively. After sIPTW, treatment duration was longer for the palbociclib group (median: 20.7 months) than the ribociclib (18.3 months) and abemaciclib (17.1 months) groups (ribociclib vs palbociclib: hazard ratio [HR]=1.12 [95% confidence interval (CI), 1.05 - 1.20], P = 0.0008; abemaciclib vs palbociclib: HR = 1.13 [95% CI, 1.05 - 1.22], P = 0.0012). Treatment durations were similar between the ribociclib and abemaciclib groups (HR = 1.01 [95% CI, 0.92 - 1.11], P = 0.8280). Twelve-month treatment discontinuation rates were higher among patients initiating ribociclib or abemaciclib, at 39.4% and 41.1%, respectively, than among patients initiating palbociclib (33.3%). In the analysis of patients who initiated palbociclib, ribociclib, or abemaciclib from 2017 onward, 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; notably, more patients initially treated with ribociclib or abemaciclib transitioned to palbociclib than those who switched oppositely. Conclusions: Treatment durations, discontinuation rates, and subsequent treatments differ between CDK4/6is for HR+/HER2- mBC in US routine clinical practice. Clinical trial registration number: NCT06495164.