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 (p<0.05 indicating significance) and I2 statistics (I2>50% 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<0.00001). Four out of 56 trials were excluded from the final analysis. The sensitivity analysis conducted in the 52 studies involving four trials with A (%2yPFS 49, CI 95% 40-59), thirty-nine trials with P (%2yPFS 48, CI 95% 45-50) and nine with R (%2yPFS 54, CI 95% 48-60) confirmed the effect size observed. In the analysis comparing the three CDK 4/6 inhibitors, no differences were observed when comparing A and P (p=0.751) or A and R (p=0.376), but a possible difference was observed when comparing R and P (p=0.045). Conclusion: This analysis did not reveal significant differences in 2-year rwPFS, the primary outcome in most real-world studies, among the CDK4/6 inhibitors. Any observed differences between R and P should be interpreted with consideration for the patient characteristics within the studies analysed. Further adjustment of the analysis using multiple variables is planned to assess inter-trial differences and mitigate bias inherent in real-world settings. Citation Format: L. Moscetti, I. Sperduti, S. Zaniboni, L. Belluzzi, E. Zattarin, L. Cortesi, P. Vici, F. Piacentini, C. Omarini, E. Barbieri, F. Canino, M. Barbolini, F. Caggia, M. Dominici, A. Toss. 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]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS5-05-30.