Aburaki Riona, Fujiwara Yu, Haketa Saya, Horita Nobuyuki
Department of Medicine, Yokohama City University School of Medicine, Japan.
Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
J Natl Cancer Inst. 2025 Jul 24. doi: 10.1093/jnci/djaf190.
Immune checkpoint inhibitor (ICI) has improved survival outcomes in patients with resectable non-small cell lung cancer (NSCLC). Recent clinical trials have evaluated several ICI strategies including neoadjuvant-only chemoimmunotherapy, neoadjuvant-adjuvant (perioperative) chemoimmunotherapy, adjuvant-only chemoimmunotherapy, and ICI single- and dual-therapy. However, the optimal perioperative approach remains unclear.
As a systematic review, databases were searched to identify eligible randomized controlled trials (RCTs) evaluating perioperative treatment incorporating at least one ICI as perioperative therapy for resectable NSCLC. A random model network meta-analysis was performed. All statistical tests were two-sided.
Eleven RCTs with 4,532 patients were included in the analysis. Seven perioperative strategies were compared; however, some were not comparable due to the presence of independent loops. The addition of adjuvant ICI therapy to neoadjuvant chemoimmunotherapy was not associated with improved event-free survival (EFS) (Hazard Ratio [HR] 0.97, 95% confidence interval [95% CI] 0.67-1.41, p = .87) or overall survival (HR 1.17, 95% CI 0.59-2.31, p = .65). When comparing adjuvant-only chemoimmunotherapy to neoadjuvant-only and perioperative chemoimmunotherapy, both neoadjuvant-only and perioperative strategies showed numerically longer OS compared to adjuvant-only chemoimmunotherapy, although the differences were not statistically significant. Regarding safety, the addition of ICI treatment to neoadjuvant chemoimmunotherapy did not significantly increase the incidence of any-grade, grade 3-5, or grade 5 TRAEs.
No clear benefit was observed for adding adjuvant ICI therapy to neoadjuvant chemoimmunotherapy. Further research is needed to directly compare neoadjuvant-only vs perioperative chemoimmunotherapy, and to determine the optimal number of cycles and duration of ICI treatment for patients with resectable NSCLC.
免疫检查点抑制剂（ICI）改善了可切除非小细胞肺癌（NSCLC）患者的生存结局。近期临床试验评估了多种ICI策略，包括仅新辅助化疗免疫治疗、新辅助-辅助（围手术期）化疗免疫治疗、仅辅助化疗免疫治疗以及ICI单药和双药治疗。然而，最佳围手术期治疗方法仍不明确。
作为一项系统评价，检索数据库以识别评估围手术期治疗的合格随机对照试验（RCT），这些试验将至少一种ICI作为可切除NSCLC的围手术期治疗。进行随机模型网络荟萃分析。所有统计检验均为双侧检验。
分析纳入了11项RCT，共4532例患者。比较了7种围手术期策略；然而，由于存在独立环，一些策略无法进行比较。在新辅助化疗免疫治疗基础上加用辅助ICI治疗与无事件生存期（EFS）改善无关（风险比[HR] 0.97，95%置信区间[95%CI] 0.67 - 1.41，p = 0.87）或总生存期（HR 1.17，95%CI 0.59 - 2.31，p = 0.65）。当比较仅辅助化疗免疫治疗与仅新辅助和围手术期化疗免疫治疗时，与仅辅助化疗免疫治疗相比，仅新辅助和围手术期策略的总生存期在数值上更长，尽管差异无统计学意义。关于安全性，在新辅助化疗免疫治疗中加用ICI治疗并未显著增加任何级别、3 - 5级或5级治疗相关不良事件（TRAE）的发生率。
在新辅助化疗免疫治疗基础上加用辅助ICI治疗未观察到明显益处。需要进一步研究直接比较仅新辅助与围手术期化疗免疫治疗，并确定可切除NSCLC患者ICI治疗的最佳周期数和持续时间。
