PMID- 38102891 OWN - NLM STAT- MEDLINE DCOM- 20240401 LR - 20240401 IS - 1756-5391 (Electronic) IS - 1756-5391 (Linking) VI - 17 IP - 1 DP - 2024 Mar TI - First-line CDK4/6 inhibitor-based combinations for HR+/HER2- advanced breast cancer: A Bayesian network meta-analysis. PG - 106-118 LID - 10.1111/jebm.12571 [doi] AB - BACKGROUND: International 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). METHODS: We 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. RESULTS: Thirteen 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. CONCLUSIONS: Ribociclib+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). CI - (c) 2023 Chinese Cochrane Center, West China Hospital of Sichuan University and John Wiley & Sons Australia, Ltd. FAU - Guo, Xianan AU - Guo X AUID- ORCID: 0000-0001-7631-0740 AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Zhou, Yunxiang AU - Zhou Y AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Zhang, Kun AU - Zhang K AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Lu, Wei AU - Lu W AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. AD - 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. FAU - Zhong, Xi AU - Zhong X AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Wu, Shijie AU - Wu S AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Shen, Lu AU - Shen L AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Chen, Huihui AU - Chen H AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. FAU - Chen, Yiding AU - Chen Y AD - 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. AD - Zhejiang Provincial Clinical Research Center for Cancer, Hangzhou, Zhejiang, China. AD - Cancer Center, Zhejiang University, Hangzhou, Zhejiang, China. LA - eng GR - the Preferred Foundation of Zhejiang Province Postdoctoral Research Projects/ GR - ZJ2021136/Preferred Foundation of Zhejiang Province Postdoctoral Research Projects/ PT - Journal Article PT - Meta-Analysis DEP - 20231216 PL - England TA - J Evid Based Med JT - Journal of evidence-based medicine JID - 101497477 RN - TK8ERE8P56 (ribociclib) RN - 60UAB198HK (abemaciclib) RN - 22X328QOC4 (Fulvestrant) RN - 0 (Protein Kinase Inhibitors) RN - EC 2.7.11.22 (CDK4 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) RN - 0 (Aminopyridines) RN - 0 (Benzimidazoles) RN - 0 (Purines) SB - IM MH - Humans MH - Female MH - Fulvestrant/therapeutic use MH - Network Meta-Analysis MH - *Protein Kinase Inhibitors/therapeutic use MH - *Breast Neoplasms/drug therapy MH - Cyclin-Dependent Kinase 4/therapeutic use MH - *Aminopyridines MH - *Benzimidazoles MH - *Purines OTO - NOTNLM OT - CDK4/6 inhibitors OT - HR+/HER2- advanced breast cancer OT - endocrine therapy OT - network meta-analysis EDAT- 2023/12/16 11:44 MHDA- 2024/04/01 06:42 CRDT- 2023/12/16 03:53 PHST- 2023/04/03 00:00 [received] PHST- 2023/12/04 00:00 [accepted] PHST- 2024/04/01 06:42 [medline] PHST- 2023/12/16 11:44 [pubmed] PHST- 2023/12/16 03:53 [entrez] AID - 10.1111/jebm.12571 [doi] PST - ppublish SO - J Evid Based Med. 2024 Mar;17(1):106-118. doi: 10.1111/jebm.12571. Epub 2023 Dec 16.