Comparative Analysis of the Effectiveness of CDK Inhibitors and Conventional Chemotherapy in Metastatic Breast Cancer

Metastatic breast cancer (MBC), particularly the hormone receptor–positive/HER2-negative subtype, remains an incurable disease with limited long-term therapeutic success. The advent of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has transformed the treatment landscape, yet their comparative benefit over conventional chemotherapy in real-world clinical settings remains incompletely defined. In this study, we performed a comprehensive comparative analysis of CDK4/6 inhibitors and standard chemotherapy regimens in patients with metastatic breast cancer, integrating evidence from randomized clinical trials, network meta-analyses, and real-world observational data. Outcomes assessed included progression-free survival, overall survival, treatment tolerability, and quality-of-life measures. Our findings demonstrate that CDK4/6 inhibitors, particularly when combined with endocrine therapy, consistently provide superior progression-free survival and improved tolerability compared with conventional chemotherapy, with trends toward improved overall survival in selected patient populations. Resistance mechanisms, molecular predictors of response, and the role of combination strategies targeting parallel signaling pathways are also discussed. These results support the preferential use of CDK4/6-based regimens as a cornerstone of therapy for hormone receptor–positive metastatic breast cancer and highlight the need for biomarker-driven treatment optimization to overcome therapeutic resistance.