Matching-adjusted indirect comparison of bireociclib plus fulvestrant versus abemaciclib plus fulvestrant as second-line treatment of HR+/HER2− advanced breast cancer.

Abstract

e15141 Background: Abemaciclib plus fulvestrant has demonstrated significant clinical benefit in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer who had progressed on prior endocrine therapy (MONARCH 2). Bireociclib, a novel selective CDK4/6 inhibitor, has also shown promising results in this setting (BRIGHT-2, NCT05077449). Due to the absence of head-to-head trials, we conducted an anchored matching-adjusted indirect comparison (MAIC) to evaluate the relative efficacy and safety of these two treatments. Methods: Using MAIC methodology, individual patient data from the BRIGHT-2 trial were weighted to match the published aggregate baseline characteristics from the MONARCH 2 trial. The primary outcome was investigator-assessed progression-free survival (PFS). Safety outcomes were also compared between the matched populations. Results: After matching adjustment, the effective sample size (ESS) of BRIGHT-2 trial was 121 patients. The median PFS was 19.7 months in the Bireociclib plus fulvestrant group compared with 16.4 months in the Abemaciclib plus fulvestrant group (HR = 0.877, 95%CI 0.469,1.640). In terms of safety profiles, hematological toxicities were analyzed to compare the two treatments. For laboratory abnormalities, no significant differences were observed in neutrophil count decreased (any grade: OR 1.47, 95% CI 0.844-2.552; grade 3-4: OR 1.12, 95% CI 0.761-1.649) and white blood cell count decreased (any grade: OR 0.87, 95% CI 0.517-1.469; grade 3-4: OR 1.02, 95% CI 0.661-1.573). Lymphocyte count decreased was significantly less frequent in the Bireociclib group for both any grade and grade 3-4 events (any grade: OR 0.09, 95% CI 0.056-0.155; grade 3-4: OR 0.14, 95% CI 0.045-0.471). Grade 3-4 anemia occurred more frequently in the Bireociclib group (OR 7.35, 95% CI 3.522,15.329), while the any grade incidence of anemia tended to be lower in the Bireociclib group (OR 0.67, 95% CI 0.438-1.030). Notably, while any grade diarrhea was more frequent in the Bireociclib group (OR 2.1, 95% CI 1.076-4.114), grade 3-4 diarrhea occurred significantly less frequently (OR 0.48, 95% CI 0.248-0.948) compared to the Abemaciclib group. Conclusions: This MAIC analysis suggests comparable efficacy between Bireociclib and Abemaciclib when combined with fulvestrant in patients with HR+/HER2- advanced breast cancer who progressed following prior endocrine therapy. The safety profiles of Bireociclib and Abemaciclib were generally comparable. However, Bireociclib demonstrated a lower risk of grade ≥ 3 diarrhea. Given the inherent limitations of MAIC analyses, these findings should be considered hypothesis-generating and warrant confirmation through direct comparative trials.