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.

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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.