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

BMC Medicine

Research Article

Lele Zhang¹  Haiping Zhang²  Jie Luo²  Anwen Xiong²  Chunyan Wu³  Dongliang Bian⁴  Haoran Xia⁴  Fenghuan Sun⁴  Jie Dai⁴  Nan Song⁴  Chang Chen⁴  Hongcheng Liu⁴  Ming Liu⁴  Boxiong Xie⁴  Jie Yang⁴  Wenxin He⁴  Huansha Yu⁴  Liangdong Sun⁴  Xinsheng Zhu⁴  Junjie Hu⁴  Jing Zhang⁴  Haifeng Wang⁴  Gening Jiang⁵  Liang Duan⁵  Peng Zhang⁵  Yuming Zhu⁵ 

[1] Central Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 200092, Shanghai, China;Department of Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 200092, Shanghai, China;Department of Pathology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 200092, Shanghai, China;Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 200092, Shanghai, China;Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 200092, Shanghai, China;Department of Thoracic Surgery, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, No. 507 Zhengmin Road, 200433, Shanghai, China;

关键词: Neoadjuvant chemoimmunotherapy;    Non-small-cell lung cancer;    Potentially resectable disease;    Transcriptomic characteristics;   

DOI  :  10.1186/s12916-022-02696-4

 received in 2022-03-14, accepted in 2022-12-05,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundThis trial aimed to analyse the safety, effectiveness and transcriptomic characteristics of neoadjuvant toripalimab plus chemotherapy in II–III non-small-cell lung cancer (NSCLC).MethodsPatient 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.ResultsIn 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).ConclusionsNeoadjuvant 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 registrationChiCTR1900024014, June 22, 2019.

【 授权许可】

CC BY   
© The Author(s) 2022

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