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

## TL;DR

This study compares abemaciclib and palbociclib for treating metastatic breast cancer and finds abemaciclib improves survival and reduces blood-related side effects.

## Contribution

This is the first real-world evidence showing abemaciclib's survival benefit over palbociclib in HR+/HER2- metastatic breast cancer.

## Key findings

- Abemaciclib was associated with longer median overall survival (6.0 vs. 5.0 years) compared to palbociclib.
- Abemaciclib had lower hematologic toxicity (39.2% vs 54.2%) but higher diarrhea rates (24.6% vs 19.7%).
- The survival benefit was confirmed across multiple sensitivity and subgroup analyses.

## Abstract

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.

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.

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.

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.

•Abemaciclib showed superior OS vs palbociclib (median 6.0 vs 5.0 years)•Lower composite hematologic toxicity with abemaciclib (39.2 % vs 54.2 %)•Higher diarrhea with abemaciclib (24.6 % vs 19.7 %), hospitalizations not increased•Survival benefit confirmed in on-treatment and landmark sensitivity analyses

Abemaciclib showed superior OS vs palbociclib (median 6.0 vs 5.0 years)

Lower composite hematologic toxicity with abemaciclib (39.2 % vs 54.2 %)

Higher diarrhea with abemaciclib (24.6 % vs 19.7 %), hospitalizations not increased

Survival benefit confirmed in on-treatment and landmark sensitivity analyses