Abstract
BACKGROUND: CDK4/6 inhibitors plus aromatase inhibitors (AI) significantly improve the therapeutic effect of initial treatment for HR + /HER2- advanced breast cancer. However, there is a lack of head-to-head randomized controlled trials involving the four CDK4/6 inhibitors in current clinical treatments. This article aims to compare the efficacy and safety of the four CDK4/6 inhibitors in previously untreated HR + /HER2- advanced breast cancer for a better clinical medication selection. METHODS: We performed a systematic search on databases published up to May 19, 2024 in the PubMed, Embase, and Cochrane library, and we focused on the data of phase II/III trials that met inclusion criteria. Pooled data on progression-free survival (PFS), objective response rate (ORR), clinical benefit rate (CBR), all adverse events (AE), and 3/4 adverse events were analyzed using the fixed-effect consistency models. RESULTS: Dalpiciclib plus AI showed the best survival benefit in PFS (SUCRA value 77.9%) for all patients. In terms of ORR and CBR, Abemaciclib plus AI were ranked the best benefit (89.3% and 68.9%, respectively). Furthermore, Abemaciclib plus AI was ranked at the top for prolonging PFS in majority of the subgroups. In terms of AEs and grade 3/4 AEs, dalpiciclib plus AI had the greatest probability (91.3% and 99.8%). Ribociclib plus AI had lowest adverse events (29.3%), and grade 3/4 adverse events of abemaciclib plus AI were the least (26.2%). CONCLUSION: There was no statistically significant difference in PFS among the four CDK4/6 inhibitors. Dalpiciclib has the best therapeutic effect in PFS. Meanwhile, dalpiciclib has the highest risk of adverse events and the 3/4 adverse events incidence compared with the others.