Kim Kun, Sweeting Michael, Jönsson Linus, Wilking Nils
Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
Nordic HTA, AstraZeneca Nordic AB, Stockholm, Sweden.
Thorac Cancer. 2025 Jan;16(1):e15535. doi: 10.1111/1759-7714.15535.
The long-term real-world effect of immunotherapy (IO) is uncertain in metastatic nonsmall cell lung cancer (mNSCLC). This retrospective observational study aimed to describe treatment patterns following the introduction of IO, estimate real-world treatment effects of IO compared to standard of care, and evaluate the impact of introduction of IO on a real-world population, based on a large dataset of over 10 000 patients with several years of follow-up.
Data from routine care of lung cancer patients were extracted from Flatiron Health including those who received either IO or platinum-based doublet chemotherapy (PBDC) in the first line (1L), or either IO or chemotherapy (CT) in the second line (2L). Real-world overall survival (rwOS) and real-world time to next therapy (rwTTNT) were estimated using Cox regression. Flexible parametric models, relaxing proportional hazard assumptions, were used to evaluate long-term IO effects.
After 1:1 nearest neighbor matching among 16 754 1L and 6548 2L patients, the hazard ratio (HR) was 0.942 (95% CI, 0.902-0.984) in 1L and 0.853 (95% CI, 0.795-0.915) in 2L. Adjusting for crossover effects, HR was 0.887 in 1L and 0.775 in 2L. Over the 7-year follow-up, the mean rwOS benefit was 3.2 months for 1L and 2.7 months for 2L. IO significantly delayed rwTTNT in both 1L and 2L. The IO effects increased and persisted over time, with uncertainty in the time-varying HR estimate.
IO improves survival in patients with mNSCLC, though the effect size is smaller than in trials and long-term survival estimates are uncertain.
免疫疗法（IO）在转移性非小细胞肺癌（mNSCLC）中的长期真实世界疗效尚不确定。这项回顾性观察性研究旨在描述IO引入后的治疗模式，评估IO与标准治疗相比的真实世界治疗效果，并基于一个超过10000例患者且有多年随访的大型数据集，评估IO引入对真实世界人群的影响。
从Flatiron Health提取肺癌患者常规护理数据，包括一线（1L）接受IO或铂类双联化疗（PBDC），或二线（2L）接受IO或化疗（CT）的患者。使用Cox回归估计真实世界总生存期（rwOS）和真实世界至下次治疗时间（rwTTNT）。采用灵活参数模型，放宽比例风险假设，以评估IO的长期效果。
在16754例1L患者和6548例2L患者中进行1:1最近邻匹配后，1L的风险比（HR）为0.942（95%CI，0.902-0.984），2L为0.853（95%CI，0.795-0.915）。调整交叉效应后，1L的HR为0.887，2L为0.775。在7年随访中，1L的平均rwOS获益为3.2个月，2L为2.7个月。IO在1L和2L中均显著延迟了rwTTNT。IO的效果随时间增加并持续存在，时变HR估计存在不确定性。
IO可改善mNSCLC患者的生存期，尽管效应大小小于试验中的效应大小，且长期生存估计尚不确定。
