PMID- 31970560 OWN - NLM STAT- MEDLINE DCOM- 20201027 LR - 20201027 IS - 1573-7217 (Electronic) IS - 0167-6806 (Linking) VI - 180 IP - 1 DP - 2020 Feb TI - Cyclin-dependent kinase 4 and 6 inhibitors in hormone receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer: a meta-analysis of randomized clinical trials. PG - 21-32 LID - 10.1007/s10549-020-05528-2 [doi] AB - BACKGROUND: Breakthrough progress has been made in Cyclin-Dependent kinase 4 and 6 (CDK4/6) inhibitors when combined with endocrine therapy (ET) for hormone receptor-positive (HR+), HER2-negative (HER2-) advanced breast cancer (ABC). Though significant improvements of progression-free survival (PFS) for CDK4/6 inhibitors were demonstrated, however, the results of overall survival (OS) profile were not consistent. This study is conducted to further evaluate the efficacy and safety of CDK4/6 inhibitors for HR+ /HER2- ABC, and explore the prefer population through subgroup analysis. METHOD: We identified relevant randomized controlled trials that compared CDK4/6 inhibitors plus ET to ET alone in HR+ /HER2- ABC. We calculated the hazard ratios (HRs) for PFS and OS, and risk ratios (RRs) for objective response rate (ORR), clinical benefit rate (CBR), adverse events (AEs). Statistical analysis was performed with the random-effects model. RESULT: Eight trials and 4580 patients were included in this meta-analysis. Compared to ET alone, CDK4/6 inhibitors plus ET not only produced a significantly longer PFS (HR = 0.55, 95% confidence interval [CI] 0.50-0.59, p < 0.00001), but also manifested an extension of OS (HR = 0.79, 95% CI 0.67-0.93, p = 0.004) for HR+ /HER2- ABC. Similarly, the benefit was also manifested in ORR (RR = 1.47, 95% CI 1.30-1.67, p < 0.00001) and CBR (RR = 1.20, 95% CI 1.12-1.30, p < 0.00001). The improvements of PFS were observed in the combined treatment group as both the first-line (HR = 0.56) and the second-line therapy (HR = 0.53), and irrespective of menopausal status, the presence of visceral metastasis, previous treatment with chemotherapy, their race or age. Nevertheless, more hematologic and gastrointestinal adverse events were observed with CDK4/6 inhibitors. The most common Grade 3-4 AEs is neutropenia (RR 31.95). CONCLUSION: Significant advantages of PFS and OS were observed for CDK4/6 inhibitors in HR+/HER2- ABC. Furthermore, the benefit of PFS was across all subgroups. Though associated with an increased occurrence of AEs, most of which are reversible, manageable, and acceptable. Therefore, CDK4/6 inhibitors could be recommended as a preferred options for patients with HR+ /HER2- ABC. FAU - Li, Jing AU - Li J AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. FAU - Fu, Fangmeng AU - Fu F AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. FAU - Yu, Liuwen AU - Yu L AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. FAU - Huang, Meng AU - Huang M AD - Fujian Center For Disease Control and Prevention, Fuzhou, 350001, China. FAU - Lin, Yuxiang AU - Lin Y AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. FAU - Mei, Qian AU - Mei Q AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. FAU - Lv, Jinxing AU - Lv J AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. FAU - Wang, Chuan AU - Wang C AUID- ORCID: 0000-0002-4451-0788 AD - Department of Breast Surgery, Fujian Medical University Union Hospital, Fuzhou, 350001, China. chuanwang1968@outlook.com. LA - eng PT - Journal Article PT - Meta-Analysis PT - Review DEP - 20200122 PL - Netherlands TA - Breast Cancer Res Treat JT - Breast cancer research and treatment JID - 8111104 RN - 0 (Antineoplastic Agents) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Receptors, Estrogen) RN - 0 (Receptors, Progesterone) RN - EC 2.7.10.1 (Receptor, ErbB-2) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 4) RN - EC 2.7.11.22 (Cyclin-Dependent Kinase 6) SB - IM MH - Antineoplastic Agents/administration & dosage/adverse effects/*therapeutic use MH - Antineoplastic Combined Chemotherapy Protocols/adverse effects/therapeutic use MH - Breast Neoplasms/*drug therapy/metabolism/pathology MH - Clinical Trials, Phase II as Topic MH - Clinical Trials, Phase III as Topic MH - Cyclin-Dependent Kinase 4/*antagonists & inhibitors MH - Cyclin-Dependent Kinase 6/*antagonists & inhibitors MH - Female MH - Humans MH - Prognosis MH - Protein Kinase Inhibitors/administration & dosage/adverse effects/*therapeutic use MH - Randomized Controlled Trials as Topic MH - Receptor, ErbB-2/metabolism MH - Receptors, Estrogen/metabolism MH - Receptors, Progesterone/metabolism MH - Treatment Outcome OTO - NOTNLM OT - Advanced breast cancer OT - CDK4/6 inhibitors OT - Hormone receptor-positive OT - Overall survival OT - Progress-free survival EDAT- 2020/01/24 06:00 MHDA- 2020/10/28 06:00 CRDT- 2020/01/24 06:00 PHST- 2019/10/14 00:00 [received] PHST- 2020/01/09 00:00 [accepted] PHST- 2020/01/24 06:00 [pubmed] PHST- 2020/10/28 06:00 [medline] PHST- 2020/01/24 06:00 [entrez] AID - 10.1007/s10549-020-05528-2 [pii] AID - 10.1007/s10549-020-05528-2 [doi] PST - ppublish SO - Breast Cancer Res Treat. 2020 Feb;180(1):21-32. doi: 10.1007/s10549-020-05528-2. Epub 2020 Jan 22.