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Published in: BMC Medicine 1/2022

Open Access 01-12-2022 | NSCLC | Research article

Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II–III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial

Authors: Xinsheng Zhu, Liangdong Sun, Nan Song, Wenxin He, Boxiong Xie, Junjie Hu, Jing Zhang, Jie Yang, Jie Dai, Dongliang Bian, Haoran Xia, Fenghuan Sun, Anwen Xiong, Jie Luo, Lele Zhang, Huansha Yu, Ming Liu, Hongcheng Liu, Haifeng Wang, Haiping Zhang, Chang Chen, Chunyan Wu, Liang Duan, Yuming Zhu, Peng Zhang, Gening Jiang

Published in: BMC Medicine | Issue 1/2022

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Abstract

Background

This trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II–III non-small-cell lung cancer (NSCLC).

Methods

Patient eligibility mainly involved treatment-naive, clinical stage II–III and wild-type EGFR/ALK NSCLC. The patients received 2–4 cycles of toripalimab (240 mg q3w) plus carboplatin-based chemotherapy. After the second treatment cycle, all patients were re-evaluated by a multidisciplinary team. Candidates eligible for surgery underwent surgery; otherwise, patients received the remaining treatment cycles. The primary endpoints were safety and major pathological response (MPR). Secondary endpoints were R0 resection rate, progression-free survival (PFS) and overall survival (OS). RNA sequencing of baseline and post-treatment samples was conducted to explore the transcriptomic characteristics of the therapeutic response.

Results

In total, 50 eligible patients were enrolled, including 12 (24.0%) with resectable disease (RD) and 38 (76.0%) with potentially resectable disease (PRD). Treatment-related adverse events (TRAEs) were recorded in 48 cases (96.0%). Severe TRAEs occurred in 3 (6.0%) cases, including myelosuppression, drug-induced liver injury and death related to haemoptysis. The objective response rate (ORR) was 76.0%, with 8 (16.0%) patients having a complete response (CR), 30 (60.0%) partial response (PR), 10 (20.0%) stable disease (SD) and 2 (4.0%) progressive disease (PD). Surgery could be achieved in 12 (100%) patients with RD and 25 (65.8%) with PRD; 1 (2.0%) with PRD refused surgery. Therefore, R0 resection was performed for all 36 (100%) patients who underwent surgery; 20 (55.6%) achieved MPR, including 10 (27.8%) with a complete pathological response (pCR). The CHI3L1 (chitinase-3-like protein 1) immunohistochemistry (IHC) expression of baseline tumour samples could predict the therapeutic response (AUC=0.732), OS (P=0.017) and PFS (P=0.001). Increased PD-1 expression, T cell abundance and immune-related pathway enrichment were observed in post-treatment samples compared to baseline in the response group (CR+PR) but not in the non-response group (SD+PD).

Conclusions

Neoadjuvant toripalimab plus chemotherapy was safe and effective, with a high MPR and manageable TRAEs for II–III NSCLC, even converting initially PRD to RD. Disparate transcriptomic characteristics of therapeutic efficiency were observed, and CHI3L1 expression predicted therapeutic response and survival.

Trial registration

ChiCTR1900024014, June 22, 2019.
Appendix
Available only for authorised users
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Metadata
Title
Safety and effectiveness of neoadjuvant PD-1 inhibitor (toripalimab) plus chemotherapy in stage II–III NSCLC (LungMate 002): an open-label, single-arm, phase 2 trial
Authors
Xinsheng Zhu
Liangdong Sun
Nan Song
Wenxin He
Boxiong Xie
Junjie Hu
Jing Zhang
Jie Yang
Jie Dai
Dongliang Bian
Haoran Xia
Fenghuan Sun
Anwen Xiong
Jie Luo
Lele Zhang
Huansha Yu
Ming Liu
Hongcheng Liu
Haifeng Wang
Haiping Zhang
Chang Chen
Chunyan Wu
Liang Duan
Yuming Zhu
Peng Zhang
Gening Jiang
Publication date
01-12-2022
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2022
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-022-02696-4

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