IPD meta-analysis of phase 3 trials of endocrine therapy with or without CDK4/6 inhibitors for HR-positive, HER2-negative advanced breast cancer

An individual patient data meta-analysis of phase 3 randomized controlled trials evaluated the survival impact of addition of CDK4/6 inhibitors to endocrine therapy (ET) in patients with HR-positive, HER2-negative advanced breast cancer (HR+ HER2- aBC). In the literature through June 2, 2025, the authors identified 11 phase 3 trials, including 6035 patients and four agents (abemaciclib, ribociclib, palbociclib, and dalpiciclib). CDK4/6 inhibitors plus ET significantly improved progression-free survival compared with ET monotherapy, both in endocrine-sensitive cancers (HR 0.57; p<0.001) and in endocrine-resistant cancers (HR 0.51; p<0.001). CDK4/6 inhibitors plus ET also improved overall survival compared with ET monotherapy, both in endocrine-sensitive cancers (HR HR 0.83; p=0.0005) and endocrine-resistant cancer (HR 0.77; p=0.003). All individual agents plus ET showed PFS benefits over ET alone; however, only abemaciclib and ribociclib showed significant OS benefits. The benefit of addition of CDK4/6 inhibitors to ET was observed in clinically relevant subgroups. The authors conclude that CDK4/6 inhibitors plus endocrine therapy significantly improved survival in HR+ HER2- aBC.