Work

After a CDK4/6 Inhibitor: State of the Art in Hormone Receptor–Positive Metastatic Breast Cancer

Year: 2025

Type: article

Abstract: CDK 4/6 inhibitors (CDK4/6i) remain part of the standard first-line treatment for patients with hormone receptor–positive metastatic breast cancer, offering demonstrable improvements in both progression-free survival and overall survival. However, resistance inevitably develops, and the optimal treatment sequencing after CDK4/6i progression remains undefined. Tumor heterogeneity and diverse resistance mechanisms—including alterations in ESR1 and PIK3CA —complicate treatment decisions in the post-CDK4/6i setting. Genomic profiling has helped to characterize these and other clinically relevant alterations, uncovering new avenues for therapeutic intervention. Building on these insights, a growing number of novel endocrine agents, phosphoinositide-3-kinase/AKT pathway–targeted therapies, and antibody-drug conjugates (ADCs) have demonstrated efficacy in biomarker-selected populations and are reshaping the treatment landscape beyond CDK4/6i progression. This chapter reviews current standards of care, emerging therapeutic options, and evolving combination strategies across biomarker-defined subgroups. We also highlight how ongoing clinical trials and advances in molecular profiling are informing personalized approaches to overcome endocrine resistance and improve patient outcomes.

Source: American Society of Clinical Oncology Educational Book

DOI: 10.1200/edbk-25-473372