Comparative real-world progression free survival of CDK4/6 inhibitors in HR+/HER2- breast cancer patients with bone metastases

Background: The introduction of CDK4/6 inhibitors (CDK4/6i) has improved outcomes in hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer (mBC), including in patients with bone metastases. Assessing their comparative effectiveness in real-world settings is crucial. Methods: This retrospective, multicenter cohort study (January 2019–December 2023; median follow-up 39 months) evaluated the real-world progression-free survival (rwPFS) of abemaciclib, ribociclib, and palbociclib combined with endocrine therapy (ET) in HR+/HER2- mBC patients with bone metastases. Overall survival (OS) was a secondary exploratory endpoint. A total of 1399 patients with ECOG PS 0–1 and at least 12 months of follow-up were included. Analyses used propensity score matching (PSM) and inverse probability of treatment weighting (IPTW) to adjust for confounding. Results: Palbociclib showed shorter rwPFS (22 months) compared to abemaciclib (32 months; HR = 1.47, p = 0.001) and ribociclib (35 months; HR = 1.49, p < 0.001). No significant difference was observed between abemaciclib and ribociclib. OS was also lower with palbociclib (47 months) versus abemaciclib (60 months; HR = 1.77, p < 0.001) and ribociclib (64 months; HR = 1.69, p = 0.001). Results were consistent after PSM and IPTW adjustment. CONCLUSION: Ribociclib and abemaciclib may provide superior rwPFS and OS compared to palbociclib in HR+/HER2- mBC patients with bone metastases.