Xie Ning, Qin Tao, Ren Wei, Yao Herui, Yu Yunfang, Hong Huangming
Department of Medical Oncology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Guangzhou, People's Republic of China.
Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People's Republic of China.
Cancer Manag Res. 2020 Jun 4;12:4241-4250. doi: 10.2147/CMAR.S254365. eCollection 2020.
To assess the efficacy and safety of cyclin-dependent kinases 4 and 6 inhibitors (CDKi) combined with endocrine therapy (ET) in women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (ABC) and compare the efficacy of different CDKi (palbociclib, ribociclib, or abemaciclib).
This study based on randomized Phase 2 or 3 trials of CDKi plus ET compared with placebo plus ET for women with HR+/HER2-ABC and identify relevant randomized clinical trials (RCTs) published prior to February 2020. The primary endpoint was progression-free survival (PFS), the secondary endpoints included overall survival (OS), objective response rate (ORR), clinical benefit response (CBR) and safety. The PROSPERO registry number is 42018081105.
The results from eight trials including 4580 participants were pooled. Evidence indicated that the PFS of CDKi group was significantly prolonged (hazard ratio [HR] 0.55, 95% confidence interval [CI] 0.50-0.60, P < 0.01) compared with placebo group. The ORR and CBR were better (risk ratio [RR] 1.47, 95% CI 1.30-1.67, P < 0.01; 1.24, 95% CI 1.15-1.35, P < 0.01) in the CDKi group. The OS of CDKi group (HR 0.75, 95% CI 0.67-0.85, P < 0.01) was significantly longer than ET alone. Subgroup analyses confirmed that the benefit was consistent across most subgroups. Subgroup analyses showed no statistically significant difference of PFS among three CDKi: palbociclib vs ribociclib (HR 0.55, 95% CI 0.49-0.60, P = 0.34), palbociclib vs abemaciclib (HR 0.53, 95% CI, 0.47-0.59, P = 0.61), and ribociclib vs abemaciclib (HR 0.56, 95% CI, 0.51-0.62, P = 0.72). Treatment-related grade 3 or 4 hematologic adverse events (AEs) were more frequently in CDKi group.
CDKi combined with ET can significantly prolong PFS and improve the ORR, CBR and OS in patients with HR+/HER2- ABC. However, the advantage of different CDKi has not been established.
评估细胞周期蛋白依赖性激酶4和6抑制剂（CDKi）联合内分泌治疗（ET）用于激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性的晚期乳腺癌（ABC）女性患者的疗效和安全性，并比较不同CDKi（帕博西尼、瑞博西尼或阿贝西利）的疗效。
本研究基于CDKi加ET与安慰剂加ET用于HR+/HER2-ABC女性患者的随机2期或3期试验，并识别2020年2月之前发表的相关随机临床试验（RCT）。主要终点为无进展生存期（PFS），次要终点包括总生存期（OS）、客观缓解率（ORR）、临床获益反应（CBR）和安全性。国际前瞻性注册系统（PROSPERO）注册号为42018081105。
汇总了八项试验的结果，共4580名参与者。证据表明，与安慰剂组相比，CDKi组的PFS显著延长（风险比[HR]0.55，95%置信区间[CI]0.50-0.60，P<0.01）。CDKi组的ORR和CBR更好（风险比[RR]1.47，95%CI 1.30-1.67，P<0.01；1.24，95%CI 1.15-1.35，P<0.01）。CDKi组的OS（HR 0.75，95%CI 0.67-0.85，P<0.01）显著长于单纯ET组。亚组分析证实，大多数亚组的获益是一致的。亚组分析显示，三种CDKi之间的PFS无统计学显著差异：帕博西尼与瑞博西尼（HR 0.55，95%CI 0.49-0.60，P=0.34）、帕博西尼与阿贝西利（HR 0.53，95%CI 0.47-0.59，P=0.61）以及瑞博西尼与阿贝西利（HR 0.56，95%CI 0.51-0.62，P=0.72）。CDKi组治疗相关的3级或4级血液学不良事件（AE）更常见。
CDKi联合ET可显著延长HR+/HER2-ABC患者的PFS，并改善ORR、CBR和OS。然而，不同CDKi的优势尚未明确。
