Venugopal Natasha, Vazquez-Urrutia Jorge Raul, Zhu Junjia, Hashinokuchi Asato, Takamori Shinkichi, Komiya Takefumi
Department of Medicine, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.
Department of Public Health Sciences, Penn State College of Medicine, Hershey, PA, USA.
Ann Surg Oncol. 2025 Jul 17. doi: 10.1245/s10434-025-17766-z.
Currently, atezolizumab and pembrolizumab are standard management for curatively resected stage II-III non-small cell lung cancer (NSCLC) owing to prior studies showing that they improve disease-free survival. However, these studies excluded the planned use of adjuvant radiation therapy. Survival benefit of adding immune checkpoint inhibitor (ICI) in patients treated with adjuvant chemoradiation (CT+RT) has not been fully assessed.
Using National Cancer Database (NCDB), we identified and, based on therapy received, stratified 4,934 cases involving patients undergoing complete resection with pathologic stage II-IIIB NSCLC who survived at least 1 month without neoadjuvant CT or RT and subsequently received adjuvant chemotherapy. Kaplan-Meier methods and multi-variable Cox regression models were used for survival analysis. Propensity score matching was performed to compare adjuvant CT+RT+ICI vs. CT+RT. A p-value of <0.05 was considered statistically significant.
The addition of ICI to adjuvant CT improved overall survival (OS) (2-year OS 90.1% vs. 86%, univariate and multivariate hazard ratios [HRs] 0.72 and 0.66, p = 0.0024 and 0.0003, respectively). However, no OS benefit was seen in those who received adjuvant CT+RT (2-year OS 77.8% vs. 76.1%, univariate and multivariate HRs 0.83 and 0.85, p = 0.3677 and 0.4369, respectively). Propensity score matching analysis showed similar results (2-year OS 77.8% vs. 79.6%, univariate and multivariate HRs 0.91 and 0.87, p = 0.7143 and 0.5868, respectively).
Our retrospective real-world analysis suggests that adjuvant ICIs do not improve survival outcome when combined with adjuvant CT+RT. This result mirrors recent negative trials studying ICI+CT+RT in unresectable stage III NSCLC and limited-stage SCLC. Further investigations are warranted.
目前，阿替利珠单抗和帕博利珠单抗是治愈性切除的II - III期非小细胞肺癌（NSCLC）的标准治疗方案，因为先前的研究表明它们可改善无病生存期。然而，这些研究排除了辅助放疗的计划使用。在接受辅助放化疗（CT + RT）的患者中添加免疫检查点抑制剂（ICI）的生存获益尚未得到充分评估。
利用国家癌症数据库（NCDB），我们识别并根据接受的治疗，对4934例接受了病理II - IIIB期NSCLC完全切除、未接受新辅助CT或RT且存活至少1个月并随后接受辅助化疗的患者进行分层。采用Kaplan - Meier方法和多变量Cox回归模型进行生存分析。进行倾向评分匹配以比较辅助CT + RT + ICI与CT + RT。p值<0.05被认为具有统计学意义。
在辅助CT中添加ICI可改善总生存期（OS）（2年OS为90.1%对86%，单变量和多变量风险比[HRs]分别为0.72和0.66，p分别为0.0024和0.0003）。然而，接受辅助CT + RT的患者未观察到OS获益（2年OS为77.8%对76.1%，单变量和多变量HRs分别为0.83和0.85，p分别为(0.3677)和(0.4369)）。倾向评分匹配分析显示了类似结果（2年OS为77.8%对79.6%，单变量和多变量HRs分别为0.91和0.87，p分别为0.7143和0.5868）。
我们的回顾性真实世界分析表明，辅助ICI与辅助CT + RT联合使用时并不能改善生存结局。这一结果与最近在不可切除的III期NSCLC和局限期SCLC中研究ICI + CT + RT的阴性试验结果一致。有必要进行进一步研究。
