Continuing cyclin-dependent kinase 4/6 inhibition in metastatic breast cancer patients previously treated with another cyclin-dependant kinase 4/6 inhibitor: a protocol for systematic review and meta-analysis

Abstract Background: Breast cancer is the most common cancer among women worldwide. Most breast cancers are estrogen receptor-positive and epidermal growth factor receptor 2 negative (ER+/HER2-). A small proportion of these cases are metastatic, and cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors are the mainstay of treatment in this scenario. Evidence supports the existence of differences between the three approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in preclinical and clinical settings. However, literature regarding the use of a CDK4/6i in metastatic breast cancer patients (MBC) previously treated with another CDK4/6i is scarce. Methods: A search will be performed on the PubMed, Embase, and Web of Science databases following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. In addition, a manual search of the San Antonio Breast Cancer Conference, American Society of Clinical Oncology annual conference, European Society of Medical Oncology annual conference, and European Society of Medical Oncology Breast annual conference will be conducted. Discussion: To our knowledge, no previous systematic review has evaluated the available evidence regarding the efficacy and safety of CDK4/6i treatment in MBC previously treated with another CDK4/6i. This systematic review and meta-analysis will synthesise existing data on the effectiveness and safety of using a CDK4/6i after prior exposure to another in MBC. It will also identify gaps in the literature for potential future research. The results of this study will focus on multiple audiences including patients, their families, caregivers, and healthcare professionals. These results will be published in a peer-reviewed journal. Systematic review registration: PROSPERO CRD42022330355