PMID- 38212842 OWN - NLM STAT- MEDLINE DCOM- 20240206 LR - 20240212 IS - 1741-7015 (Electronic) IS - 1741-7015 (Linking) VI - 22 IP - 1 DP - 2024 Jan 12 TI - A network meta-analysis of efficacy and safety for first-line and second/further-line therapies in postmenopausal women with hormone receptor-positive, HER2-negative, advanced breast cancer. PG - 13 LID - 10.1186/s12916-023-03238-2 [doi] LID - 13 AB - BACKGROUND: Hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR + /HER2 -) advanced breast cancer is a prevalent subtype among postmenopausal women. Despite the growing number of randomized clinical trials (RCTs) exploring this topic, the efficacy and safety of first-line and second/further-line treatments remain uncertain. Accordingly, our aim was to conduct a comprehensive evaluation of the efficacy and safety of these therapies through network meta-analysis. METHODS: RCTs were identified by searching Pubmed, Embase, and major cancer conferences. The efficacy of interventions was assessed using the hazard ratios (HRs) of progression-free survival (PFS) and overall survival (OS), while safety was indicated by the incidence of any grade adverse events (AEs), grade 3-5 AEs, AEs leading to treatment discontinuation, and AEs leading to death. Both time-variant HRs fractional polynomial models and time-invariant HRs Cox-proportional hazards models were considered for handling time-to-event data. Safety indicators were analyzed using Bayesian network meta-analysis. Additionally, subgroup analyses were conducted based on patient characteristics. RESULTS: A total of 41 RCTs (first-line 17, second/further-lines 27) were included in the analysis. For first-line treatment, the addition of Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrine therapy significantly improved therapeutic efficacy in terms of both PFS and OS, demonstrating the best performance across all mechanisms. Specifically, the combination of Abemaciclib and Letrozole demonstrated the most favorable performance in terms of PFS, while Ribociclib plus Fulvestrant yielded the best outcomes in OS. Incorporating the immune checkpoint inhibitor Avelumab into the regimen with CDK4/6 inhibitors and selective estrogen receptor degraders significantly enhanced both PFS and OS in second-line or later treatments. Regarding safety, endocrine monotherapy performed well. Regarding safety, endocrine monotherapy performed well. There is mounting evidence suggesting that most CDK4/6 inhibitors may demonstrate poorer performance with respect to hematologic AEs. However, additional evidence is required to further substantiate these findings. CONCLUSIONS: CDK4/6 inhibitors, combined with endocrine therapy, are pivotal in first-line treatment due to their superior efficacy and manageable AEs. For second/further-line treatment, adding immune checkpoint inhibitors to CDK4/6 inhibitors plus endocrine therapy may produce promising results. However, to reduce the results' uncertainty, further trials comparing these novel treatments are warranted. TRIAL REGISTRATION: Registration number: PROSPERO (CRD42022377431). CI - (c) 2023. The Author(s). FAU - Shao, Hanqiao AU - Shao H AD - School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. AD - Center for Pharmacoeconomics and Outcomes Research & Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. FAU - Zhao, Mingye AU - Zhao M AD - School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. AD - Center for Pharmacoeconomics and Outcomes Research & Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. FAU - Guan, Ai-Jia AU - Guan AJ AD - Department of Rehabilitation Medicine, West China Hospital, Sichuan University, Sichuan, China. FAU - Shao, Taihang AU - Shao T AD - School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. AD - Center for Pharmacoeconomics and Outcomes Research & Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. FAU - Zhou, Dachuang AU - Zhou D AD - School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. AD - Center for Pharmacoeconomics and Outcomes Research & Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. FAU - Yu, Guo AU - Yu G AD - School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, China. guoyu@cpu.edu.cn. FAU - Tang, Wenxi AU - Tang W AD - School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. tokammy@cpu.edu.cn. AD - Center for Pharmacoeconomics and Outcomes Research & Department of Public Affairs Management, School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, Jiangsu, China. tokammy@cpu.edu.cn. LA - eng GR - BK20200005/Natural Science Foundation of Jiangsu Province for Distinguished Young Scholars/ GR - 72174207/Innovative Research Group Project of the National Natural Science Foundation of China/ PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't DEP - 20240112 PL - England TA - BMC Med JT - BMC medicine JID - 101190723 RN - 7LKK855W8I (Letrozole) RN - EC 2.7.10.1 (Receptor, ErbB-2) SB - IM MH - Female MH - Humans MH - Antineoplastic Combined Chemotherapy Protocols/therapeutic use MH - *Breast Neoplasms/metabolism MH - Letrozole/therapeutic use MH - Network Meta-Analysis MH - *Postmenopause MH - Receptor, ErbB-2 PMC - PMC10785354 OTO - NOTNLM OT - Advanced breast cancer OT - Efficacy OT - HR-positive/HER2-negative OT - Network meta-analysis OT - Safety COIS- The authors declare that they have no competing interests. EDAT- 2024/01/12 00:42 MHDA- 2024/01/15 12:43 PMCR- 2024/01/12 CRDT- 2024/01/11 23:41 PHST- 2023/05/18 00:00 [received] PHST- 2023/12/19 00:00 [accepted] PHST- 2024/01/15 12:43 [medline] PHST- 2024/01/12 00:42 [pubmed] PHST- 2024/01/11 23:41 [entrez] PHST- 2024/01/12 00:00 [pmc-release] AID - 10.1186/s12916-023-03238-2 [pii] AID - 3238 [pii] AID - 10.1186/s12916-023-03238-2 [doi] PST - epublish SO - BMC Med. 2024 Jan 12;22(1):13. doi: 10.1186/s12916-023-03238-2.