First Clinical Medical School, Fujian Medical University, Fuzhou, China.
Department of Medical Oncology, Xiamen Cancer Hospital, The First Affiliated Hospital of Xiamen University, Xiamen, China.
PLoS One. 2020 Jun 4;15(6):e0233571. doi: 10.1371/journal.pone.0233571. eCollection 2020.
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).
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).
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.
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.
本荟萃分析旨在评估细胞周期蛋白依赖性激酶（CDK）4/6 抑制剂联合内分泌治疗（ET）在激素受体阳性（HR+）、人表皮生长因子受体 2 阴性（HER2-）晚期乳腺癌（ABC）中的疗效和安全性。
我们检索了从建库到 2019 年 10 月 10 日的 PubMed、Embase、Cochrane、ClinicalTrials.gov、ASCO、ESMO 和 AACR 数据库，以纳入比较 CDK4/6 抑制剂联合 ET 与单药 ET 且不限制治疗线的随机对照试验（RCT）。主要分析的结局是无进展生存期（PFS）、总生存期（OS）、客观缓解率（ORR）、临床获益率（CBR）和不良事件（AE）。
在 938 项研究中，有 9 项 RCT 共纳入 5043 名女性，符合条件。与 ET 单药治疗相比，CDK 4/6 抑制剂联合 ET 可改善 PFS（风险比（HR）0.54，95%置信区间（CI）0.50-0.59，p<0.00001）和 OS（HR 0.77，95% CI 0.69-0.85，p<0.00001），无论 ET 策略如何（PFS 中 HR 0.54，95% CI 0.50-0.59；OS 中 HR 0.77，95% CI 0.69-0.85）、晚期疾病的治疗线（PFS 中 HR 0.52，95% CI 0.46-0.59；OS 中 HR 0.75，95% CI 0.66-0.85）和绝经状态（PFS 中 HR 0.54，95% CI 0.50-0.58；OS 中 HR 0.76，95% CI 0.68-0.84）。与 ET 组相比，联合组更易发生 3/4 级 AE（RR 2.66，95% CI 2.44-2.90，p < 0.00001）。
CDK 4/6 抑制剂联合 ET 治疗可延长 HR+/HER2-ABC 患者的生存时间。与 HR+/HER2-ABC 中的内分泌单药治疗相比，这种联合治疗是一种更好的治疗策略，无论治疗线、绝经状态和其他个体特征如何。
