PMID- 37653504 OWN - NLM STAT- MEDLINE DCOM- 20230904 LR - 20231120 IS - 1471-2407 (Electronic) IS - 1471-2407 (Linking) VI - 23 IP - 1 DP - 2023 Aug 31 TI - Comparative efficacy and safety of different combinations of three CDK4/6 inhibitors with endocrine therapies in HR+/HER-2 - metastatic or advanced breast cancer patients: a network meta-analysis. PG - 816 LID - 10.1186/s12885-023-11322-2 [doi] LID - 816 AB - BACKGROUND: This network meta-analysis aimed to assess the comparative efficacy and safety of combinations involving three cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and endocrine therapies (ETs) in patients with metastatic or advanced breast cancer (BC) who are hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-). METHODS: We initially identified relevant studies from previous meta-analyses and then conducted a comprehensive search of PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) databases to locate additional studies published between February 2020 and September 2021. Essential data were extracted, and a network meta-analysis was performed using R 4.1.1 software with a random-effects model. Furthermore, we assigned rankings to all available treatment combinations by calculating their cumulative probability. RESULTS: Data analysis included ten reports from nine studies. Pooled results demonstrated that each treatment combination significantly reduced the hazard risk of progression-free survival (PFS) compared to treatment with an aromatase inhibitor (AI) or fulvestrant alone. However, there were no differences observed in PFS or overall survival (OS) among the different treatment combinations. Additionally, patients receiving palbociclib plus AI and abemaciclib plus AI or fulvestrant experienced more severe adverse events (AEs), with hazard ratios (HRs) of 10.83 (95% confidence interval [CI] = 2.3 to 52.51) and 4.8 (95%CI = 1.41 to 16.21), respectively. The HR for ribociclib plus AI was 9.45 (95%CI = 2.02 to 43.61), and the HR for palbociclib plus fulvestrant was 6.33 (95%CI = 1.03 to 39.86). Based on the ranking probabilities, palbociclib plus fulvestrant had the highest probability of achieving superior PFS (37.65%), followed by abemaciclib plus fulvestrant (28.76%). For OS, ribociclib plus fulvestrant ranked first (34.11%), with abemaciclib plus fulvestrant in second place (25.75%). In terms of safety, palbociclib plus AI (53.98%) or fulvestrant (51.37%) had the highest probabilities of being associated with adverse events. CONCLUSIONS: Abemaciclib plus fulvestrant or ribociclib plus AI appear to be effective and relatively safe for the treatment of HR+/HER2- metastatic or advanced BC patients. However, given the reliance on limited evidence, our findings require further validation through additional studies. CI - (c) 2023. BioMed Central Ltd., part of Springer Nature. FAU - Liu, Yiyuan AU - Liu Y AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Wu, Jinyao AU - Wu J AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Ji, Zeqi AU - Ji Z AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Chen, Lingzhi AU - Chen L AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Zou, Juan AU - Zou J AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Zheng, Jiehua AU - Zheng J AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Lin, Weixun AU - Lin W AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Cai, Jiehui AU - Cai J AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Chen, Yaokun AU - Chen Y AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Zheng, Daitian AU - Zheng D AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. FAU - Chen, Yexi AU - Chen Y AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. yxchen3@stu.edu.cn. FAU - Li, Zhiyang AU - Li Z AD - Department of Thyroid, Breast and Hernia Surgery, The Second Affiliated Hospital of Shantou, University Medical College, Shantou, Guangdong, China. s_zyli4@stu.edu.cn. LA - eng GR - 210728156901524, 210728156901519/the Special Fund Project of Guangdong Science and Technology/ GR - 210728156901524, 210728156901519/the Special Fund Project of Guangdong Science and Technology/ GR - A2021432, B2021448/Medical Scientific Research Foundation of Guangdong Province, China/ GR - A2021432, B2021448/Medical Scientific Research Foundation of Guangdong Province, China/ GR - 210521236491457, 210625106490696/Shantou Medical Science and Technology Planning Project/ GR - 210521236491457, 210625106490696/Shantou Medical Science and Technology Planning Project/ GR - 31/38/47/54/the Undergraduate Innovation Training Project of Shantou University/ GR - 31/38/47/54/the Undergraduate Innovation Training Project of Shantou University/ PT - Journal Article PT - Meta-Analysis DEP - 20230831 PL - England TA - BMC Cancer JT - BMC cancer JID - 100967800 RN - TK8ERE8P56 (ribociclib) RN - 60UAB198HK (abemaciclib) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - 22X328QOC4 (Fulvestrant) RN - 0 (Aromatase Inhibitors) RN - EC 2.7.11.22 (CDK4 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) SB - IM MH - Humans MH - Female MH - *Breast Neoplasms/drug therapy MH - Fulvestrant MH - Network Meta-Analysis MH - Aromatase Inhibitors MH - Cyclin-Dependent Kinase 4 PMC - PMC10469949 OTO - NOTNLM OT - Abemaciclib OT - Breast cancer OT - Network meta-analysis OT - Palbociclib OT - Ribociclib COIS- The authors declare no conflict of interest. EDAT- 2023/09/01 00:41 MHDA- 2023/09/04 06:42 PMCR- 2023/08/31 CRDT- 2023/08/31 23:53 PHST- 2022/10/12 00:00 [received] PHST- 2023/08/20 00:00 [accepted] PHST- 2023/09/04 06:42 [medline] PHST- 2023/09/01 00:41 [pubmed] PHST- 2023/08/31 23:53 [entrez] PHST- 2023/08/31 00:00 [pmc-release] AID - 10.1186/s12885-023-11322-2 [pii] AID - 11322 [pii] AID - 10.1186/s12885-023-11322-2 [doi] PST - epublish SO - BMC Cancer. 2023 Aug 31;23(1):816. doi: 10.1186/s12885-023-11322-2.