Background:CDK4/6-inhibitors have demonstrated similar efficacy and are considered an effective first-line endocrine treatment of patients with hormone-receptor positive (HR+)/human-epidermal-growth-factor-receptor-2 negative (HER2−) metastatic breast cancer (MBC) in the endpoint of progression-free survival (PFS). Amongst these, palbociclib was first to achieve regulatory approval, followed subsequently by ribociclib and abemaciclib. However, recent updates of overall survival (OS) showed inconsistencies in the OS benefit for palbociclib compared with the other two CDK4/6-inhibitors. With the lack of head-to-head comparison studies, our study sought to compare indirect survival outcomes between CDK4/6-inhibitors in this setting using a novel reconstructive algorithm.Methods:Phase III randomized trials comparing first-line aromatase inhibitor with/without a CDK4/6-inhibitor in post-menopausal patients with HR+/HER2− MBC were identified through systemic review and literature search of online archives of published manuscripts and conference proceedings. A graphical reconstructive algorithm was utilized to retrieve time-to-event data from reported Kaplan-Meier OS and PFS plots to allow for comparison of survival outcomes. Survival analyses were conducted with Cox proportional-hazards model with a shared-frailty term.Results:Three randomized phase III trials—PALOMA-2, MONALEESA-2 and MONARCH-3—comprising 1827 patients were included. Indirect pairwise comparisons of all CDK4/6-inhibitors showed no significant PFS differences (allp> 0.05). Likewise, indirect treatment comparison between ribociclib vs. palbociclib (one-stage: HR = 0.903, 95%-CI: 0.746–1.094,p= 0.297), abemaciclib vs. palbociclib (one-stage: HR = 0.843, 95%-CI: 0.690–1.030,p= 0.094) and abemaciclib vs. ribociclib (one-stage: HR = 0.933, 95%-CI: 0.753–1.157,p= 0.528) failed to demonstrate a significant OS difference.Conclusions:Findings from this indirect treatment comparison suggest no significant PFS or OS differences between CDK4/6-inhibitors in post-menopausal patients with HR+/HER2− MBC.
背景：在激素受体阳性（HR+）/人表皮生长因子受体2阴性（HER2−）转移性乳腺癌（MBC）患者的一线内分泌治疗中，CDK4/6抑制剂在无进展生存期（PFS）终点上显示出相似的疗效，被视为有效的治疗选择。其中，哌柏西利率先获得监管批准，随后是瑞博西利和阿贝西利。然而，近期更新的总生存期（OS）数据显示，哌柏西利相较于其他两种CDK4/6抑制剂的OS获益存在不一致性。由于缺乏头对头比较研究，本研究旨在通过一种新型重建算法，间接比较CDK4/6抑制剂在此背景下的生存结局。 方法：通过系统综述及对已发表手稿和会议记录的在线文献库进行检索，筛选出在绝经后HR+/HER2− MBC患者中比较一线芳香化酶抑制剂联合或不联合CDK4/6抑制剂的三期随机试验。采用图形重建算法从已报告的Kaplan-Meier OS和PFS曲线中提取时间-事件数据，以进行生存结局比较。生存分析采用带有共享脆弱性项的Cox比例风险模型。 结果：共纳入三项三期随机试验——PALOMA-2、MONALEESA-2和MONARCH-3，涉及1827名患者。所有CDK4/6抑制剂间的间接两两比较均未显示显著的PFS差异（所有p > 0.05）。同样，瑞博西利对比哌柏西利（单阶段：HR = 0.903，95% CI：0.746–1.094，p = 0.297）、阿贝西利对比哌柏西利（单阶段：HR = 0.843，95% CI：0.690–1.030，p = 0.094）以及阿贝西利对比瑞博西利（单阶段：HR = 0.933，95% CI：0.753–1.157，p = 0.528）的间接治疗比较均未能证明显著的OS差异。 结论：本间接治疗比较的结果表明，在绝经后HR+/HER2− MBC患者中，不同CDK4/6抑制剂之间在PFS或OS方面无显著差异。
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