Toripalimab plus platinum-doublet chemotherapy as perioperative therapy for initially unresectable NSCLC: An open-label, phase 2 trial.

IF 12.8 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Med Pub Date : 2025-01-30 DOI:10.1016/j.medj.2025.100574

Liang Zeng, Huan Yan, Wenjuan Jiang, Haoyue Qin, Jiacheng Dai, Yuda Zhang, Shiyou Wei, Shanmei Chen, Li Liu, Yi Xiong, Haiyan Yang, Yizhi Li, Zhan Wang, Li Deng, Qinqin Xu, Ling Peng, Ruiguang Zhang, Chao Fang, Xue Chen, Jun Deng, Jing Wang, Ting Li, Hong Liu, Gao Zhang, Nong Yang, Yongchang Zhang

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引用次数: 0

Abstract

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.

查看原文本刊更多论文

托利哌单抗加铂双药化疗作为最初不可切除的NSCLC围手术期治疗：一项开放标签的2期试验。

背景：托利哌单抗联合化疗围手术期治疗可切除的II-IIIA期非小细胞肺癌（NSCLC）是安全有效的；然而，对于这种治疗方案是否能将不可切除的NSCLC转化为可切除的，我们知之甚少。方法：本研究招募了40例初始不可切除的IIIA-IIIB期NSCLC患者。托利哌单抗（240 mg）和铂双药化疗每3周给药，共2-4个周期。评估诱导治疗效果后决定手术切除。主要观察指标为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、主要病理反应（MPR）和病理完全缓解（pCR）。可用的基线肿瘤活检样本用于分子生物标志物分析，包括大量RNA测序和多重免疫染色。该研究已在ClinicalTrials.gov注册：NCT04144608。结果：在40例接受诱导多利帕利单抗联合化疗的患者中，29例（72.5%）患者接受了手术，全部实现了R0切除（100% R0率）。在这些患者中，17例（58.6%）达到MPR， 10例（34.5%）患者评估为pCR。中位随访时间为31.8个月（95%可信区间[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患者在基线时生发中心B细胞（三级淋巴结构[TLS]的特征）的基因集表达较高，这表明患者的TLS状态与免疫治疗反应的诱导有关。结论：托里帕利单抗诱导治疗最初不可切除的NSCLC具有较高的R0率和MPR率，具有良好的安全性和令人鼓舞的生存结果。基金资助：本工作由国家自然科学基金资助。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Med MEDICINE, RESEARCH & EXPERIMENTAL-

CiteScore

17.70

自引率

0.60%

发文量

102

期刊介绍： Med is a flagship medical journal published monthly by Cell Press, the global publisher of trusted and authoritative science journals including Cell, Cancer Cell, and Cell Reports Medicine. Our mission is to advance clinical research and practice by providing a communication forum for the publication of clinical trial results, innovative observations from longitudinal cohorts, and pioneering discoveries about disease mechanisms. The journal also encourages thought-leadership discussions among biomedical researchers, physicians, and other health scientists and stakeholders. Our goal is to improve health worldwide sustainably and ethically. Med publishes rigorously vetted original research and cutting-edge review and perspective articles on critical health issues globally and regionally. Our research section covers clinical case reports, first-in-human studies, large-scale clinical trials, population-based studies, as well as translational research work with the potential to change the course of medical research and improve clinical practice.