Real-world effectiveness of CDK4/6 inhibitor re-treatment in HR+/HER2- metastatic breast cancer.

Abstract

e13039 Background: The postMONARCH trial showed modest progression-free survival (PFS) improvement with abemaciclib after progression on ribociclib/palbociclib among patients with HR+/HER2- mBC. Real-world evidence is limited by single-center data and lack of appropriate comparators. This study assessed real-world effectiveness of abemaciclib compared to endocrine therapy (ET) monotherapy to complement evidence from the postMONARCH trial. Methods: This retrospective cohort study used the US-based, electronic health record-derived deidentified Flatiron Health Research Database to analyze patients with HR+/HER2- mBC who received second-line or later treatment with either abemaciclib±ET or ET monotherapy (2020-2025) following documented progression on first-line palbociclib-/ribociclib-based therapy. In the treatment cohort, abemaciclib was allowed to be sequential (without intervening ET) or non-sequential (with intervening ET monotherapy). In the comparison group, multiple consecutive ET monotherapy lines were allowed. Descriptive statistics were used to compare baseline characteristics and treatment patterns. PFS and overall survival (OS) from second-line initiation were analyzed using time-varying multivariable Cox models. Interaction and stratified analyses were conducted to assess potential effect modification by baseline ECOG status. Results: Among 411 patients (177 abemaciclib, 234 ET monotherapy), 97% received abemaciclib as second-line therapy. Baseline characteristics were generally comparable, with similar first-line CDK4/6i use and ECOG distribution (~80% ECOG 0-1). The abemaciclib group was younger (median age 63 vs. 68 years). Abemaciclib was associated with longer median PFS (7.9 vs. 3.7 months) and OS (31.0 vs. 9.3 months) than ET monotherapy (both log-rank p < 0.001). In adjusted time-varying Cox models, abemaciclib reduced risk of progression (aHR 0.49, 95% CI: 0.39-0.62) and death (aHR 0.37, 95% CI: 0.28-0.49). Stratified analysis by ECOG showed consistent relative treatment effect of abemaciclib vs. ET monotherapy within ECOG strata (PFS: aHR 0.51 in ECOG 0-1 vs. 0.58 in ECOG 2-4; OS: 0.37 vs. 0.34, respectively). Survival benefit of abemaciclib was observed among patients with poor ECOG performance status. Interaction analysis found no evidence that ECOG modified the association between abemaciclib and OS (p = 0.482). Conclusions: Abemaciclib-based CDK4/6i rechallenge was associated with improved survival compared with ET monotherapy following progression on prior palbociclib/ribociclib. Abemaciclib maintained a relative survival benefit compared with ET monotherapy among patients with poor performance status. These findings support the potential utility of abemaciclib-based CDK4/6i rechallenge, including among patients with reduced performance status who are typically excluded from clinical trials (e.g., postMONARCH).