托瑞帕利单抗联合铂类双药化疗作为初始不可切除非小细胞肺癌围手术期治疗：一项开放标签的2期试验。
Toripalimab plus platinum-doublet chemotherapy as perioperative therapy for initially unresectable NSCLC: An open-label, phase 2 trial.
作者信息
Zeng Liang, Yan Huan, Jiang Wenjuan, Qin Haoyue, Dai Jiacheng, Zhang Yuda, Wei Shiyou, Chen Shanmei, Liu Li, Xiong Yi, Yang Haiyan, Li Yizhi, Wang Zhan, Deng Li, Xu Qinqin, Peng Ling, Zhang Ruiguang, Fang Chao, Chen Xue, Deng Jun, Wang Jing, Li Ting, Liu Hong, Zhang Gao, Yang Nong, Zhang Yongchang
机构信息
Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
Department of Pathology, Hunan Cancer Hospital and The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China.
出版信息
Med. 2025 Jun 13;6(6):100574. doi: 10.1016/j.medj.2025.100574. Epub 2025 Jan 31.
BACKGROUND
Perioperative treatment with toripalimab combined with chemotherapy was efficacious and safe in resectable stage II-IIIA non-small cell lung cancer (NSCLC); however, little is known about whether this treatment regimen could convert unresectable NSCLC to resectable.
METHODS
This study enrolled 40 treatment-naive patients with initially unresectable stage IIIA-IIIB NSCLC. Toripalimab (240 mg) and platinum-doublet chemotherapy were administered every 3 weeks for 2-4 cycles. Surgical resection was decided after assessing the efficacy of induction therapy. The primary outcome was the R0 resection rate. The secondary outcomes included safety, overall survival, disease-free survival, event-free survival, objective response rate, major pathological response (MPR), and pathological complete response (pCR). Available baseline tumor biopsy samples were used for molecular biomarker analyses, including bulk RNA sequencing and multiplex immunostaining. This study was registered at ClinicalTrials.gov: NCT04144608.
FINDINGS
Of the 40 patients who received induction toripalimab plus chemotherapy, 29 (72.5%) patients received surgery, and all achieved R0 resection (100% R0 rate). Of these patients, 17 (58.6%) achieved MPR, with 10 (34.5%) patients evaluated as pCR. With a median follow-up of 31.8 months (95% confidence interval [CI]: 24.2-39.4), the median event-free survival and overall survival were not reached. Molecular analyses revealed highly expressed gene sets for germinal center B cells (signatures of tertiary lymphoid structure [TLS]) at baseline among patients with pCR compared to patients with non-pCR, suggesting that the TLS status of the patients was associated with the induction of immunotherapy responses.
CONCLUSIONS
Toripalimab-based induction treatment of initially unresectable NSCLC yielded a high R0 rate and MPR rate, with a good safety profile and encouraging survival outcomes.
FUNDING
This work was funded by the National Natural Science Foundation of China.
背景
托瑞帕利单抗联合化疗的围手术期治疗在可切除的II-IIIA期非小细胞肺癌（NSCLC）中疗效显著且安全；然而，对于这种治疗方案能否将不可切除的NSCLC转化为可切除，目前知之甚少。
方法
本研究纳入了40例初治的最初不可切除的IIIA-IIIB期NSCLC患者。每3周给予托瑞帕利单抗（240mg）和铂类双联化疗，共2-4个周期。在评估诱导治疗的疗效后决定是否进行手术切除。主要结局是R0切除率。次要结局包括安全性、总生存期、无病生存期、无事件生存期、客观缓解率、主要病理缓解（MPR）和病理完全缓解（pCR）。利用可用的基线肿瘤活检样本进行分子生物标志物分析，包括全转录组RNA测序和多重免疫染色。本研究已在ClinicalTrials.gov注册：NCT04144608。
结果
在40例接受诱导托瑞帕利单抗加化疗的患者中，29例（72.5%）接受了手术，且均实现了R0切除（R0切除率为100%）。在这些患者中，17例（58.6%）达到MPR，10例（34.5%）患者评估为pCR。中位随访31.8个月（95%置信区间[CI]：24.2-39.4），中位无事件生存期和总生存期均未达到。分子分析显示，与非pCR患者相比，pCR患者基线时生发中心B细胞的基因集高度表达（三级淋巴结构[TLS]特征），这表明患者的TLS状态与免疫治疗反应的诱导有关。
结论
基于托瑞帕利单抗对最初不可切除的NSCLC进行诱导治疗，可产生较高的R0切除率和MPR率，安全性良好，生存结局令人鼓舞。
资助
本研究由中国国家自然科学基金资助。
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