92 Abemaciclib After Abemaciclib: A Real-World Comparative Analysis Challenging the Paradigm of Sequential CDK4/6 Inhibitors in Metastatic Breast Cancer

Background

Guideline-recommended first-linetreatment for hormone receptor–positive/HER2-negative (HR+/HER2−) metastatic breast cancer consists of CDK4/6 inhibitor (CDK4/6i) plus endocrine therapy (ET). Upon progression, second-line options include a CDK4/6i plus fulvestrant for patients without previous CDK4/6i exposure. Recent data, including MAINTAIN and postMONARCH, demonstrated benefit of continued CDK4/6i suppression with a distinct agent (eg, palbociclib followed by ribociclib or abemaciclib). However, evidence supporting sequential retreatment with the same CDK4/6i is limited. Therefore, real-world outcomes of patients with metastatic breast cancer receiving an abemaciclib-containing regimen in first line and second line (retreated) were compared with those receiving a non-abemaciclib CDK4/6i-containing regimen (ribociclib/palbociclib) in first line and an abemaciclib-containing regimen in second line (switched).

Methods

This retrospective cohort study utilized the Flatiron Health Research Database from January 2011 to December 2024. Eligible patients were 18 years or older, treated with a CDK4/6i-containing regimen in first line for metastatic breast cancer, had evidence of disease progression in first line, and were treated with an abemaciclib-containing regimen in second line for metastatic breast cancer (index date). Inverse probability of treatment weighting was used to balance baseline characteristics between groups. Real-world progression-free survival (rwPFS) and real-world overall survival (rwOS) were estimated from the index date (second-line start date) using Kaplan-Meier methods. Descriptive analyses and multivariate Cox regression models (hazard ratio [HR] and 95% confidence intervals [CIs]) were reported and compared across groups.

Results

Among the 447 eligible patients (retreated, n = 81; switched, n = 366 [82.8% palbociclib; 12.0% ribociclib]), the median age was 62.0 years, 64.0% were White, 67.6% were postmenopausal, and 56.6% had visceral metastasis. Retreated were less likely to receive fulvestrant in first line compared with switched (8.6% vs 20.5%, P < .05). Abemaciclib plus fulvestrant was the most common second-line regimen (63.0% retreated; 66.1% switched). Retreated patients appeared to have a more aggressive disease course prior to second-line therapy, as suggested by a shorter, unadjusted first-line treatment duration (13.3 vs 18.8 months) and shorter median rwPFS during first line (8.0 vs 13.7 months; P < .05 for both values), compared with patients who were switched. Despite this higher risk patient population, median rwPFS and rwOS at index (second line) were not statistically significantly different between patients retreated with abemaciclib vs those who switched their CDK4/6i. These results remained consistent after adjusting for potential confounders (Table).

Conclusion

This is the first real-world comparative effectiveness analysis to show that patients retreated sequentially with abemaciclib do not have statistically different second-line real-world outcomes compared with patients who switched to abemaciclib after treatment with a different CDK4/6i. Findings were consistent with postMONARCH (median PFS: 6.0 months). Overall, real-world results suggest that retreatment with abemaciclib is a viable option after progression, allowing for flexible sequencing in patients with metastatic breast cancer.