Overall survival of CDK4/6-inhibitors-based treatments in clinically relevant subgroups of metastatic breast cancer: systematic review and meta-analysis

Background: Cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors + endocrine therapy (ET) prolonged progression-free survival as first- or second-line therapy for hormone receptor-positive (HR+)/HER2-negative metastatic breast cancer prognosis. Given the recent publication of overall survival (OS) data for the 3 CDK4/6-inhibitors, we performed a meta-analysis to identify a more precise and reliable benefit from such treatments in specific clinical subgroups. Methods: We conducted a systematic literature search to select all available phase II or III randomized clinical trials of CDK4/6-inhibitors + ET reporting OS data in first- or second-line therapy of HR+/HER2-negative pre- or postmenopausal metastatic breast cancer. A random effect model was applied for the analyses. Heterogeneity was assessed with I2statistic. Subgroup analysis was performed to explore the effect of study-level factors. The project was registered in the Open Science Framework database (doi: 10.17605/OSF.IO/TNZQP)....