Guan Xin, Li Mengyuan, Ji Xinyue, Wang Yufei, Tian Lei
School of International Pharmaceutical Business, China Pharmaceutical University, Nanjing, China.
Center for Pharmacoeconomics and Outcomes Research, China Pharmaceutical University, Nanjing, China.
Front Pharmacol. 2024 Aug 5;15:1369420. doi: 10.3389/fphar.2024.1369420. eCollection 2024.
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. 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. 6 randomized controlled trials with 2,638 patients were included. The first-order FP model ( = -1) and the first-order FP model ( = 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). 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.
细胞周期蛋白依赖性激酶（CDK）4和6抑制剂（阿贝西利、哌柏西利和瑞博西利）在中国已被推荐用于激素受体阳性（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，评估CDK4/6抑制剂的疗效和安全性。通过预设的检索策略，系统检索了初治HR+晚期乳腺癌患者的II期或III期随机对照试验。分数多项式（FP）模型用于放宽比例风险假设并获得时变风险比（HR）。从预测的无进展生存期（PFS）和总生存期（OS）曲线的曲线下面积（AUC）计算无进展生存年数（PFLYs）和生存年数（LYs），以评估长期疗效获益。分析≥3级不良事件的比值比（OR）以评估安全性结局。纳入了6项随机对照试验，共2638例患者。分别使用一阶FP模型（=-1）和一阶FP模型（=1）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，阿贝西利获得了3.059个PFLYs和6.275个LYs的PFS获益。哌柏西利获得了2.302个PFLYs和6.351个LYs。瑞博西利获得了2.636个PFLYs和6.543个LYs。在安全性方面，使用CDK4/6抑制剂导致不良事件风险更高（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）。在初治HR+晚期乳腺癌患者中使用CDK4/6抑制剂可显著提高生存率，但也增加了不良事件风险。阿贝西利和瑞博西利可能分别是延长初治患者PFS和OS的最佳选择。
