Affiliation:
1. Department of Breast Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Sciences) The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China
2. Zhejiang Provincial Clinical Research Center for Cancer Hangzhou Zhejiang China
3. Cancer Center Zhejiang University Hangzhou Zhejiang China
4. Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention China National Ministry of Education Key Laboratory of Molecular Biology in Medical Sciences) The Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou Zhejiang China
Abstract
AbstractBackgroundInternational guidelines recommend cyclin‐dependent kinase 4/6 inhibitor (CDK4/6i)‐based first‐line therapy for hormone receptor‐positive, human epidermal growth factor receptor 2‐negative (HR+/HER2−) advanced breast cancer (ABC). However, direct drug comparisons are lacking. We aimed to identify the most effective and safe therapy through network meta‐analysis (NMA).MethodsWe searched PubMed, Embase, Web of Science, Cochrane Central Register of Controlled Trials, and OpenGrey up to September 30, 2023. Eligible studies included randomized controlled trials (RCTs) assessing endocrine therapy alone or in combination with CDK4/6i as first‐line endocrine treatment for HR+/HER2− ABC patients. The hazard ratios for progression‐free survival (PFS) and overall survival (OS) and relative risks for objective response rate and adverse events (AEs) were available in selected trials. We performed a Bayesian NMA following PRISMA guidelines.ResultsThirteen RCTs, involving 10 treatments, were included. Most studies were at low risk of bias. Regarding PFS, ribociclib+fulvestrant ranked first with a surface under the cumulative ranking curve (SUCRA) of 85.0%, followed by dalpiciclib+nonsteroidal aromatase inhibitor (NSAI) (SUCRA = 78.9%). Considering OS, the top three ranked treatments were ribociclib+fulvestrant (SUCRA = 94.1%), abemaciclib+NSAI (SUCRA = 69.9%), and ribociclib+NSAI (SUCRA = 68.5%). Out of four CDK4/6is, ribociclib minimized the grade 3/4 AEs, while dalpiciclib demonstrated the worst safety. Publication bias could not be ignored in our analyses, and the certainty of evidence was downgraded primarily due to imprecision.ConclusionsRibociclib+fulvestrant probably represents the best option in a first‐line setting. When combined with NSAI, dalpiciclib likely showed the best efficacy but the worst safety. Abemaciclib+NSAI and ribociclib+NSAI could also be promising treatments, while palbociclib presented inferiority. (PROSPERO Registration No. CRD42022370271)
Subject
Health Policy,General Medicine