Abstract PS5-05-30: Cycline Dipendent Kinase inhibitors 4/6 and endocrine therapy in the first line of treatment for HR+Her2- advanced breast cancer: a meta-analysis of the published real-world studies

Abstract Background: First-line treatment for HR+/HER2- advanced breast cancer (ABC) is based on CDK4/6 inhibitors (CDK4/6i) and endocrine therapy (ET). The three available CDK4/6i – palbociclib (P), abemaciclib (A), and ribociclib (R) – demonstrated comparable efficacy in pivotal Phase III trials in terms of progression-free survival (PFS). However, only R achieved a significant overall survival (OS) benefit. Most previous analyses comparing these CDK4/6i focused on efficacy, safety, and tolerability, generally showing no significant differences. Limited real-world (RW) data exist regarding inter-drug comparisons in the RW setting. Methods: We conducted a meta-analysis of the RW studies in the first-line HR+/HER2- ABC setting (with P, A, and R) to assess potential outcome differences between the three drugs. A systematic literature search was performed using PubMed with the terms: "breast cancer," "real world," "palbociclib," "abemaciclib," "ribociclib” “dalpiciclib”. Treatment comparisons utilized as effect size the percentage (%) of 2-years real-world PFS (rwPFS) and 95% confidence intervals (CI). The % of 2-year rwPFS (%2yPFS) was estimated from the median rwPFS for this analysis Heterogeneity was assessed using the χ2 Q test (p50% considered significant). The pooled effect size estimate was calculated with a random-effect model using the 2-year PFS as endpoint. Results: 67 studies were identified 56 reported the median rwPFS as the primary outcome, one reported time to next treatment (TTNT), 8 reported time to chemotherapy or time to treatment discontinuation, 2 did not reported any outcome. Considering 56 studies involving four CDK4/6 inhibitors reporting rwPFS, no significant differences were observed when comparing all three drugs (%2yPFS 49, 95% IC 46-51, p=0.39). High heterogeneity was observed across the included studies (I2=81%, p