PMID- 32497134 OWN - NLM STAT- MEDLINE DCOM- 20200821 LR - 20200821 IS - 1932-6203 (Electronic) IS - 1932-6203 (Linking) VI - 15 IP - 6 DP - 2020 TI - Combination cyclin-dependent kinase 4/6 inhibitors and endocrine therapy versus endocrine monotherapy for hormonal receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: A systematic review and meta-analysis. PG - e0233571 LID - 10.1371/journal.pone.0233571 [doi] LID - e0233571 AB - PURPOSE: This meta-analysis aimed to assess the efficacy and safety of cyclin-dependent kinase (CDK) 4/6 inhibitors plus endocrine therapy (ET) in hormonal receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). METHODS: We searched PubMed, Embase, Cochrane, ClinicalTrials.gov., ASCO, ESMO and AACR databases from inception to October 10, 2019 for randomized controlled trials (RCTs) that compared CDK 4/6 inhibitors plus ET to single-agent ET with no treatment-line restriction. The main outcomes analyzed were progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). RESULTS: Of 938 identified studies, 9 RCTs with 5043 women were eligible and included. Compared with ET alone, CDK 4/6 inhibitors and ET combination improved in PFS (hazard ratio (HR) 0.54, 95% confidence interval (CI) 0.50-0.59, p< 0.00001) and OS (HR 0.77, 95% CI 0.69-0.85, p< 0.00001), regardless of ET strategies (HR 0.54, 95% CI 0.50-0.59 in PFS; HR 0.77, 95% CI 0.69-0.85 in OS), treatment line of advanced disease (HR 0.52, 95% CI 0.46-0.59 in PFS; HR 0.75, 95% CI 0.66-0.85 in OS) and menopausal status (HR 0.54, 95% CI 0.50-0.58 in PFS; HR 0.76, 95% CI 0.68-0.84 in OS). Higher risk of grade 3/4 AEs (RR 2.66, 95% CI 2.44-2.90, p < 0.00001) were observed in the combination group than in the ET group. CONCLUSIONS: Combination therapy with CDK 4/6 inhibitors and ET prolongs survival in HR+/ HER2- ABC. This combination is a better therapeutic strategy than endocrine monotherapy in HR+/HER2- ABC, regardless of treatment line, menopausal status and other individual characteristics. FAU - Zheng, Jiani AU - Zheng J AD - First Clinical Medical School, Fujian Medical University, Fuzhou, China. AD - Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. AD - Laboratory, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. FAU - Wu, Jingxun AU - Wu J AD - First Clinical Medical School, Fujian Medical University, Fuzhou, China. AD - Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. AD - Laboratory, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. FAU - Wang, Chunyue AU - Wang C AD - First Clinical Medical School, Fujian Medical University, Fuzhou, China. AD - Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. AD - Laboratory, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. FAU - Zhuang, Shiwen AU - Zhuang S AD - First Clinical Medical School, Fujian Medical University, Fuzhou, China. AD - Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. AD - Laboratory, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. FAU - Chen, Jianbo AU - Chen J AD - First Clinical Medical School, Fujian Medical University, Fuzhou, China. AD - Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. AD - Laboratory, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. FAU - Ye, Feng AU - Ye F AUID- ORCID: 0000-0002-9159-7767 AD - First Clinical Medical School, Fujian Medical University, Fuzhou, China. AD - Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. AD - Laboratory, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China. LA - eng PT - Journal Article PT - Meta-Analysis PT - Research Support, Non-U.S. Gov't PT - Systematic Review DEP - 20200604 PL - United States TA - PLoS One JT - PloS one JID - 101285081 RN - 0 (Antineoplastic Agents, Hormonal) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Receptors, Estrogen) RN - EC 2.7.10.1 (ERBB2 protein, human) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 2.7.11.22 (CDK4 protein, human) RN - EC 2.7.11.22 (CDK6 protein, human) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 6) SB - IM MH - Adult MH - Antineoplastic Agents, Hormonal/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/*therapeutic use MH - Breast Neoplasms/*drug therapy/*metabolism MH - Cyclin-Dependent Kinase 4/*antagonists & inhibitors MH - Cyclin-Dependent Kinase 6/*antagonists & inhibitors MH - Female MH - Humans MH - Middle Aged MH - Progression-Free Survival MH - Protein Kinase Inhibitors/adverse effects/*therapeutic use MH - Receptor, ErbB-2/*metabolism MH - Receptors, Estrogen/*metabolism PMC - PMC7272037 COIS- The authors have declared that no competing interests exist. EDAT- 2020/06/05 06:00 MHDA- 2020/08/22 06:00 PMCR- 2020/06/04 CRDT- 2020/06/05 06:00 PHST- 2020/02/26 00:00 [received] PHST- 2020/05/07 00:00 [accepted] PHST- 2020/06/05 06:00 [entrez] PHST- 2020/06/05 06:00 [pubmed] PHST- 2020/08/22 06:00 [medline] PHST- 2020/06/04 00:00 [pmc-release] AID - PONE-D-20-05530 [pii] AID - 10.1371/journal.pone.0233571 [doi] PST - epublish SO - PLoS One. 2020 Jun 4;15(6):e0233571. doi: 10.1371/journal.pone.0233571. eCollection 2020.