Rugo H S, Layman R M, Lynce F, Liu X, Li B, McRoy L, Cohen A B, Estevez M, Curigliano G, Brufsky A
University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, USA.
The University of Texas MD Anderson Cancer Center, Houston, USA.
ESMO Open. 2025 Jan;10(1):104103. doi: 10.1016/j.esmoop.2024.104103. Epub 2025 Jan 3.
Randomized controlled trials have shown inconsistent overall survival (OS) benefit among the three cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) as first-line (1L) treatment of patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) metastatic breast cancer (mBC). Several real-world studies compared CDK4/6i effectiveness, with inconsistent findings. This study compared overall survival (OS) of patients with HR+/HER2- mBC receiving 1L palbociclib, ribociclib, or abemaciclib, in combination with an aromatase inhibitor (AI), in US clinical practice.
This retrospective study used real-world data from the Flatiron Health electronic health record-derived deidentified longitudinal database. Patients with HR+/HER2- mBC aged ≥18 years at mBC diagnosis started 1L CDK4/6i therapy (index treatment) between February 2015 and November 2023, with a potential ≥6-month follow-up. OS was defined as months from start of index treatment to death. Stabilized inverse probability of treatment weighting (sIPTW; primary analysis) was used to balance baseline patient characteristics. Multivariable Cox proportional hazards model was carried out as a sensitivity analysis.
Of 9146 eligible patients, 6831, 1279, and 1036 received palbociclib plus AI, ribociclib plus AI, or abemaciclib plus AI, respectively. After sIPTW, baseline characteristics were balanced between treatment groups. After sIPTW, no significant OS differences were found between treatment groups [ribociclib versus palbociclib: adjusted hazard ratio (aHR) 0.98, 95% confidence interval (CI) 0.87-1.10, P = 0.7531; abemaciclib versus palbociclib: aHR 0.95, 95% CI 0.84-1.08, P = 0.4292; abemaciclib versus ribociclib: aHR 0.97, 95% CI 0.82-1.14, P = 0.6956]. Sensitivity analysis including a subanalysis of patients who started index treatment in 2017 or later also showed no significant OS differences between treatment groups.
This large real-world study suggested that there were no significant OS differences between 1L ribociclib, abemaciclib, and palbociclib in combination with an AI for patients with HR+/HER2- mBC. These findings together with other factors such as safety and quality of life are helpful in the selection of CDK4/6i combination therapy for patients with HR+/HER2- mBC.
随机对照试验表明，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（1L）治疗中，三种细胞周期蛋白依赖性激酶4/6抑制剂（CDK4/6i）的总生存期（OS）获益并不一致。多项真实世界研究比较了CDK4/6i的有效性，但结果并不一致。本研究比较了美国临床实践中接受1L哌柏西利、瑞博西尼或阿贝西利联合芳香化酶抑制剂（AI）治疗的HR+/HER2- mBC患者的总生存期（OS）。
这项回顾性研究使用了来自Flatiron Health电子健康记录衍生的去识别纵向数据库的真实世界数据。在2015年2月至2023年11月期间，年龄≥18岁且在mBC诊断时患有HR+/HER2- mBC的患者开始接受1L CDK4/6i治疗（索引治疗），并进行了至少6个月的随访。OS定义为从索引治疗开始到死亡的月数。采用稳定的逆概率治疗权重法（sIPTW；主要分析）来平衡患者的基线特征。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名、1279名和1036名患者接受了哌柏西利联合AI、瑞博西尼联合AI或阿贝西利联合AI治疗。经过sIPTW后，各治疗组之间的基线特征得到了平衡。经过sIPTW后，各治疗组之间未发现显著的OS差异[瑞博西尼与哌柏西利：调整后的风险比（aHR）为0.98，95%置信区间（CI）为0.87-1.10，P = 0.7531；阿贝西利与哌柏西利：aHR为0.95，95%CI为0.84-1.08，P = 0.4292；阿贝西利与瑞博西尼：aHR为0.97，95%CI为0.82-1.14，P = 0.6956]。包括对2017年或之后开始索引治疗的患者进行亚分析的敏感性分析也显示，各治疗组之间未发现显著的OS差异。
这项大型真实世界研究表明，对于HR+/HER2- mBC患者，1L瑞博西尼、阿贝西利和哌柏西利联合AI治疗在总生存期方面没有显著差异。这些发现连同其他因素，如安全性和生活质量，有助于为HR+/HER2- mBC患者选择CDK4/6i联合治疗方案。
