Rugo H S, Layman R M, Lynce F, Liu X, Li B, McRoy L, Cohen A B, Estevez M, Curigliano G, Brufsky A
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, Duarte.
The University of Texas MD Anderson Cancer Center, Houston, USA.
ESMO Open. 2025 Sep 1;10(9):105570. doi: 10.1016/j.esmoop.2025.105570.
All three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i; palbociclib, ribociclib, and abemaciclib) plus aromatase inhibitor (AI) significantly prolonged progression-free survival (PFS) versus placebo plus AI and achieved a similar reduction in risk of disease progression in randomized controlled trials (RCTs) evaluating first-line (1L) treatment of hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC). To date, there have been no head-to-head RCT data comparing CDK4/6i, and most real-world comparative effectiveness studies were limited by small sample sizes and/or short follow-up. In this analysis, we compared real-world PFS (rwPFS) in patients with HR-positive/HER2-negative mBC receiving 1L CDK4/6i plus AI in United States routine clinical practice.
P-VERIFY was a retrospective comparative effectiveness study using a US nationwide deidentified electronic health record-derived longitudinal database. Patients had HR-positive/HER2-negative mBC, were ≥18 years of age, and started 1L CDK4/6i plus AI between February 2015 and November 2023. rwPFS was defined as months from CDK4/6i plus AI initiation to disease progression or death from any cause. Stabilized inverse probability of treatment weighting (sIPTW) as primary analysis was used to balance baseline characteristics. Multivariable Cox proportional hazards model was carried out as a sensitivity analysis.
Of 9146 eligible patients, 6831, 1279, and 1036 received palbociclib, ribociclib, and abemaciclib, respectively, plus AI. Baseline characteristics were generally balanced between treatment groups after sIPTW. Median [95% confidence interval (CI)] rwPFS after sIPTW was 22.7 (21.6-23.8), 22.9 (21.0-25.6), and 22.9 (20.2-26.5) months in the palbociclib, ribociclib, and abemaciclib groups, respectively. After sIPTW, there were no significant rwPFS differences (all P > 0.05) between ribociclib versus palbociclib (adjusted hazard ratio 0.97, 95% CI 0.88-1.07), abemaciclib versus palbociclib (0.96, 0.86-1.06), and abemaciclib versus ribociclib (0.98, 0.86-1.12). Findings were generally consistent across subgroups and sensitivity analyses.
Our study, the largest real-world CDK4/6i comparative effectiveness study to date, demonstrated no significant rwPFS differences between 1L palbociclib, ribociclib, and abemaciclib, plus AI, in patients with HR-positive/HER2-negative mBC.
在评估激素受体（HR）阳性/人表皮生长因子受体2（HER2）阴性转移性乳腺癌（mBC）一线（1L）治疗的随机对照试验（RCT）中，三种细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i；哌柏西利、瑞博西尼和阿贝西利）联合芳香化酶抑制剂（AI）与安慰剂联合AI相比，显著延长了无进展生存期（PFS），并在疾病进展风险降低方面取得了相似的效果。迄今为止，尚无比较CDK4/6i的头对头RCT数据，大多数真实世界的比较有效性研究受到样本量小和/或随访时间短的限制。在本分析中，我们比较了美国常规临床实践中接受1L CDK4/6i联合AI治疗的HR阳性/HER2阴性mBC患者的真实世界PFS（rwPFS）。
P-VERIFY是一项回顾性比较有效性研究，使用美国全国性的匿名电子健康记录衍生纵向数据库。患者患有HR阳性/HER2阴性mBC，年龄≥18岁，于2015年2月至2023年11月开始接受1L CDK4/6i联合AI治疗。rwPFS定义为从开始使用CDK4/6i联合AI至疾病进展或因任何原因死亡的月数。采用稳定的逆概率治疗权重（sIPTW）作为主要分析方法来平衡基线特征。进行多变量Cox比例风险模型作为敏感性分析。
在9146名符合条件的患者中，分别有6831、1279和1036名患者接受了哌柏西利、瑞博西尼和阿贝西利联合AI治疗。sIPTW后各治疗组之间的基线特征总体平衡。sIPTW后的中位[95%置信区间（CI）]rwPFS在哌柏西利组、瑞博西尼组和阿贝西利组中分别为22.7（21.6 - 23.8）、22.9（21.0 - 25.6）和22.9（20.2 - 26.5）个月。sIPTW后，瑞博西尼与哌柏西利之间（调整后风险比0.97，95%CI 0.88 - 1.07）、阿贝西利与哌柏西利之间（0.96，0.86 - 1.06）以及阿贝西利与瑞博西尼之间（0.98，0.86 - 1.12）的rwPFS均无显著差异（所有P>0.05）。各亚组和敏感性分析的结果总体一致。
我们的研究是迄今为止最大的真实世界CDK4/6i比较有效性研究，结果表明在HR阳性/HER2阴性mBC患者中，1L哌柏西利、瑞博西尼和阿贝西利联合AI治疗的rwPFS无显著差异。
