Zhou Dong, He Jia-Ming, Yu Jun-Cheng, Li Yan-Qi, Chen Liang, Zhenge Zhi, Deng Xu-Feng, Zhang Jiao, Lu Xiao, Zheng Hong, Dai Ji-Gang
Department of Thoracic Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Cardiovascular Surgery, Xinqiao Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Int J Surg. 2025 Sep 1;111(9):6162-6171. doi: 10.1097/JS9.0000000000002714. Epub 2025 Jun 12.
Neoadjuvant chemoimmunotherapy demonstrates favorable survival outcomes and high pathological complete response (pCR) rates, but its efficacy in resectable N1/N2 nonsmall cell lung cancer (NSCLC) remains unproven. Additionally, predictive biomarkers for treatment efficacy and the relationship between lymph node status postneoadjuvant therapy and survival are unclear. This prospective study evaluates the efficacy and safety of combining penpulimab with chemotherapy for resectable N1/N2 NSCLC.
This prospective cohort study enrolled patients aged ≥18 years with resectable N1/N2 NSCLC. Patients received penpulimab, carboplatin, and paclitaxel (for squamous cell carcinoma) or pemetrexed (for adenocarcinoma) every 21 days for three cycles, followed by surgery within 6 weeks. Primary endpoint: major pathological response (MPR). Secondary endpoints: pCR, objective response rate (ORR), R0 resection rate, disease-free survival (DFS), overall survival (OS), and treatment- and surgery-related adverse events. The study was Ethics Committee-approved.
From August 2022 to August 2023, 32 patients were enrolled. The preoperative ORR was 75.0%. R0 resection was achieved in 96.9%. MPR and pCR were achieved in 51.6% and 22.6% of patients, respectively. Significant associations between pCR and Response Evaluation Criteria in Solid Tumors response categories ( P < 0.001), downstaging of nodal status ( P = 0.007), and tumor mutational burden (TMB) ( P = 0.037) were observed in our analysis. Multivariate regression analysis showed that no clinical factor other than TMB was predictive of the pCR. One-year DFS was 84.4%, and OS was 96.9%, with a median follow-up of 18 months. DFS was 100% in the MPR group versus 66.7% in the non-MPR group ( P < 0.001) and higher in the pCR group ( P = 0.0074). Nodal downstaging was observed in 50.0%, with superior survival in this group. Adverse events occurred in 93.8%, primarily fatigue, nausea, vomiting, and rashes.
This is the first report of neoadjuvant penpulimab in N1/N2 NSCLC, demonstrating efficacy, feasibility, and survival benefits, especially in patients with high tumor mutational burden.
新辅助化疗免疫疗法显示出良好的生存结果和较高的病理完全缓解（pCR）率，但其在可切除的N1/N2期非小细胞肺癌（NSCLC）中的疗效仍未得到证实。此外，治疗疗效的预测生物标志物以及新辅助治疗后淋巴结状态与生存之间的关系尚不清楚。本前瞻性研究评估了派安普利单抗联合化疗治疗可切除的N1/N2期NSCLC的疗效和安全性。
本前瞻性队列研究纳入了年龄≥18岁、可切除的N1/N2期NSCLC患者。患者每21天接受一次派安普利单抗、卡铂和紫杉醇（用于鳞状细胞癌）或培美曲塞（用于腺癌）治疗，共三个周期，随后在6周内进行手术。主要终点：主要病理缓解（MPR）。次要终点：pCR、客观缓解率（ORR）、R0切除率、无病生存期（DFS）、总生存期（OS）以及与治疗和手术相关的不良事件。该研究经伦理委员会批准。
2022年8月至2023年8月，共纳入32例患者。术前ORR为75.0%。R0切除率为96.9%。分别有51.6%和22.6%的患者实现了MPR和pCR。在我们的分析中，观察到pCR与实体瘤疗效评价标准反应类别（P<0.001）、淋巴结状态降期（P=0.007）和肿瘤突变负荷（TMB）（P=0.037）之间存在显著关联。多因素回归分析显示，除TMB外，没有其他临床因素可预测pCR。1年DFS为84.4%，OS为96.9%，中位随访时间为18个月。MPR组的DFS为100%，而非MPR组为66.7%（P<0.001），pCR组更高（P=0.0074）。50.0%的患者出现淋巴结降期，该组生存情况更佳。93.8%的患者发生不良事件，主要为疲劳、恶心、呕吐和皮疹。
这是关于派安普利单抗用于N1/N2期NSCLC新辅助治疗的首份报告，证明了其疗效、可行性和生存获益，尤其是在肿瘤突变负荷高的患者中。
