Real-world comparative effectiveness of first-line abemaciclib versus palbociclib in HR+/HER2- metastatic breast cancer: A propensity-matched retrospective analysis.

Background: In the first-line treatment of hormone receptor-positive, HER2-negative (HR+/HER2-) metastatic breast cancer (mBC), the comparative effectiveness of different cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) remains unclear due to the absence of head-to-head randomized trials. We aimed to compare the real-world outcomes of abemaciclib versus palbociclib.

Methods: We performed a retrospective, propensity-matched cohort study using the TriNetX Analytics Network database (2014-2025). The primary outcome was overall survival (OS). To ensure robust findings, the analysis was supported by multiple sensitivity tests, including restricted mean survival time (RMST) to provide a model-free effect measure, and E-value analysis to quantify the potential impact of unmeasured confounding.

Results: From 15,830 eligible patients, we created a matched cohort of 2768 patients on abemaciclib and 2768 on palbociclib. After a median follow-up of 33.7 months for the abemaciclib group and 44.2 months for the palbociclib group, treatment with abemaciclib was associated with significantly longer median OS (6.0 vs. 5.0 years; HR 0.80, 95 % CI 0.72-0.90; p < 0.001). The RMST analysis confirmed a significant survival benefit of 5.96 months over the follow-up period (p < 0.001). Abemaciclib was associated with lower rates of neutropenia but higher rates of diarrhea. The survival advantage was consistent across sensitivity and subgroup analyses.

Conclusions: In this large, real-world cohort study, first-line abemaciclib was associated with a significant overall survival benefit compared to palbociclib for patients with HR+/HER2-mBC. This finding was robust across multiple sensitivity analyses. These results provide valuable evidence to inform treatment decisions in the absence of direct randomized trial data.