Continuing cyclin dependent kinase 4/6 inhibition with abemaciclib in metastatic breast cancer patients previously treated with palbociclib or ribociclib: a protocol for systematic review and meta-analysis

Abstract

Background Breast cancer is the most frequent cancer in women worldwide. Most breast cancer cases are estrogen receptor positive and epidermal growth factor receptor 2 negative (ER+/HER2-). A small proportion of these cases are metastatic with Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors being the mainstay of treatment. Evidence supports the existence of differences between the three approved cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in both preclinical and clinical settings. Abemaciclib appears to be capable of inhibiting other targets. Senescence and apoptosis took place at an earlier time and with lower concentrations of abemaciclib compared to treatment with palbociclib or ribociclib in preclinical models. Methods A search will be performed on the PubMed, Embase, and Web of Science databases following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. 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 performed. Discussion To our knowledge, no previous systematic review has evaluated the available evidence regarding the efficacy and safety of abemaciclib in MBC previously treated with palbociclib or ribociclib. This systematic review and meta-analysis will synthesize the existing data on the effectiveness and safety of abemaciclib after prior exposure to ribociclib or palbociclib in MBC. It will also identify the gap in the literature for potential future research. The results of this study will be of interest to multiple audiences including patients, their families, caregivers, and healthcare professionals. Results will be published in a peer-reviewed journal. Systematic review registration: PROSPERO CRD42022330355