Zhao Ze-Rui, Yan Wan-Pu, Yu Xiang-Yang, Zhang Jing-Bo, Fang Yi-Fan, Ma Kai, Luo Qing-Quan, Long Hao, Chen Ke-Neng, Jiang Long
Department of Thoracic Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, China.
Key Laboratory of Carcinogenesis and Translational Research, Department of Thoracic Surgery I, Peking University Cancer Hospital and Institute, Beijing, China.
J Thorac Cardiovasc Surg. 2025 Jun;169(6):1576-1584.e3. doi: 10.1016/j.jtcvs.2024.11.028. Epub 2024 Nov 29.
In patients with resectable non-small cell lung cancer (NSCLC), immune checkpoint inhibitor (ICI)-based regimens in both neoadjuvant and perioperative settings have demonstrated a survival benefit. However, no previous study has compared the efficacy between pure neoadjuvant and perioperative approaches, especially in patients who achieve a substantial pathologic response.
In this retrospective study, patients with clinical stage II-IIIB NSCLC who achieved either a major pathologic response (MPR) or pathologic complete response (pCR) after induction ICI plus chemotherapy, followed by resection, between 2019 and 2023 were identified from multicenter databases. Inverse probability of treatment weighting-adjusted Cox regression was performed to compare disease-free survival (DFS) and overall survival (OS) between patients who received ICIs postoperatively and those who did not.
One hundred thirty-six patients who achieved pCR and 72 patients who achieved MPR were enrolled. Three-quarters of them had squamous cell cancer. The inverse probability-weighted cohort represented 208 weighted patient cases (adjuvant ICI group, n = 117; control group, n = 91). The weighted DFS and OS rates did not differ between the adjuvant ICI group and the control group (3-year DFS rate: 90.2% vs 93.2%; hazard ratio [HR], 2.47; 95% confidence interval [CI], 0.74-8.22; 3-year OS rate: 89.1% vs 93.9%; HR, 2.44; 95% CI, 0.71-8.34). Adverse events during the postoperative ICI treatment were found in 19 of 120 patients (15.8%) and led to adjuvant ICI termination in 18 patients (15.0%).
Adjuvant ICI does not improve survival in NSCLC patients who achieve pCR/MPR following neoadjuvant immunochemotherapy. A de-escalation strategy could be considered, given the adverse events associated with postoperative ICI treatment.
在可切除的非小细胞肺癌（NSCLC）患者中，新辅助和围手术期基于免疫检查点抑制剂（ICI）的治疗方案已显示出生存获益。然而，既往尚无研究比较单纯新辅助治疗和围手术期治疗方法之间的疗效，尤其是在获得显著病理缓解的患者中。
在这项回顾性研究中，从多中心数据库中识别出2019年至2023年间临床分期为II-IIIB期NSCLC患者，这些患者在诱导ICI联合化疗后达到主要病理缓解（MPR）或病理完全缓解（pCR），随后接受手术切除。采用治疗权重逆概率调整的Cox回归比较术后接受ICI治疗的患者与未接受ICI治疗的患者之间的无病生存期（DFS）和总生存期（OS）。
纳入了136例达到pCR的患者和72例达到MPR的患者。其中四分之三为鳞状细胞癌。逆概率加权队列代表208例加权患者病例（辅助ICI组，n = 117；对照组，n = 91）。辅助ICI组和对照组之间的加权DFS率和OS率无差异（3年DFS率：90.2%对93.2%；风险比[HR]，2.47；95%置信区间[CI]，0.74 - 8.22；3年OS率：89.1%对93.9%；HR，2.44；95% CI，0.71 - 8.34）。120例患者中有19例（15.8%）在术后ICI治疗期间出现不良事件，18例患者（15.0%）因不良事件导致辅助ICI治疗终止。
对于新辅助免疫化疗后达到pCR/MPR的NSCLC患者，辅助ICI并不能改善生存。鉴于术后ICI治疗相关的不良事件，可考虑采取降阶梯策略。
