目的：细胞周期蛋白依赖性激酶（CDK）4和6抑制剂（abemaciclib、palbociclib和ribociclib）已被推荐用于中国激素受体阳性（HR）乳腺癌的一线治疗。我们的研究旨在通过使用分数多项式建模方法处理生存数据来评估 CDK4/6 抑制剂的有效性和安全性。方法：通过预设的检索策略系统检索初治HR晚期乳腺癌患者的II期或III期随机对照试验。采用分数多项式（FP）模型放宽比例风险假设，获得时变风险比（HR）。根据预测无进展生存期 (PFS) 和总生存期 (OS) 曲线的曲线下面积 (AUC) 计算无进展生命年 (PFLY) 和生命年 (LY)，以评估长期疗效获益。对≥3级不良事件的比值比（OR）进行安全性结果分析。结果：纳入 6 项随机对照试验，共纳入 2,638 名患者。一阶 FP 模型 (p = -1) 和一阶 FP 模型 (p = 1) 分别用于计算 PFS 和 OS 的时变 HR。外推至 240 个月，通过计算 PFS 和 OS 曲线的 AUC，abemaciclib 获得了 3.059 PFLY 和 6.275 LY 的 PFS 获益。 Palbociclib 获得了 2.302 PFLY 和 6.351 LY。 Ribociclib 获得了 2.636 PFLY 和 6.543 LY。在安全性方面，使用CDK4/6抑制剂导致不良事件风险较高（OR = 9.84，95% CI：8.13-11.95），尤其是哌柏西利（OR = 14.04，95% CI：10.52-18.90） 。结论：在初治 HR 晚期乳腺癌患者中使用 CDK4/6 抑制剂可显着提高生存率，但也会增加不良事件的风险。 Abemaciclib 和 ribociclib 可能分别是延长初治患者 PFS 和 OS 的最佳选择。版权所有 © 2024guan、Li、Ji、Wang 和 Tian。

Objective: Cyclin-dependent kinase (CDK) 4 and 6 inhibitors (abemaciclib, palbociclib and ribociclib) have been recommended in the first-line treatment of hormone receptor-positive (HR+) breast cancer in China. Our study aims to evaluate the efficacy and safety of CDK4/6 inhibitors by processing survival data using fractional polynomial modeling methods. Methods: Phase II or III randomized controlled trials in treatment-naive HR + patients with advanced breast cancer were systematically searched through the preset search strategy. The fractional polynomial (FP) model was used to relax the proportional hazard assumption and obtain time-varying hazard ratio (HR). Progression-free life years (PFLYs) and life years (LYs) were calculated from the area under curve (AUC) of the predicted progression-free survival (PFS) and overall survival (OS) curves to evaluate the long-term efficacy benefit. Odds ratio (OR) of grade≥3 adverse events were analyzed for safety outcomes. Results: 6 randomized controlled trials with 2,638 patients were included. The first-order FP model (p = -1) and the first-order FP model (p = 1) were used to calculate the time-varying HR of PFS and OS, respectively. Extrapolating to 240 months, abemaciclib obtained a PFS benefit of 3.059 PFLYs and 6.275 LYs by calculating the AUC of the PFS and OS curves. Palbociclib obtained 2.302 PFLYs and 6.351 LYs. Ribociclib obtained 2.636 PFLYs and 6.543 LYs. In terms of safety, the use of CDK4/6 inhibitors resulted in a higher risk of adverse events (OR = 9.84, 95% CI: 8.13-11.95), especially for palbociclib (OR = 14.04, 95% CI: 10.52-18.90). Conclusion: The use of CDK4/6 inhibitors in treatment-naive patients with HR + advanced breast cancer significantly improves survival, but also increases the risk of adverse events. Abemaciclib and ribociclib may be the best options for prolonging PFS and OS in treatment-naïve patients, respectively.Copyright © 2024 Guan, Li, Ji, Wang and Tian.