Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial
Tao Jiang, Pingyang Wang, Jie Zhang, Yanqiu Zhao, Jianying Zhou, Yun Fan, Yongqian Shu, Xiaoqing Liu, Helong Zhang, Jianxing He, Guanghui Gao, Xiaoqian Mu, Zhang Bao, Yanjun Xu, Renhua Guo, Hong Wang, Lin Deng, Ningqiang Ma, Yalei Zhang, Hui Feng, Sheng Yao, Jiarui Wu, Luonan Chen, Caicun Zhou, Shengxiang Ren, Tao Jiang, Pingyang Wang, Jie Zhang, Yanqiu Zhao, Jianying Zhou, Yun Fan, Yongqian Shu, Xiaoqing Liu, Helong Zhang, Jianxing He, Guanghui Gao, Xiaoqian Mu, Zhang Bao, Yanjun Xu, Renhua Guo, Hong Wang, Lin Deng, Ningqiang Ma, Yalei Zhang, Hui Feng, Sheng Yao, Jiarui Wu, Luonan Chen, Caicun Zhou, Shengxiang Ren
Abstract
This multicenter phase-II trial aimed to investigate the efficacy, safety, and predictive biomarkers of toripalimab plus chemotherapy as second-line treatment in patients with EGFR-mutant-advanced NSCLC. Patients who failed from first-line EGFR-TKIs and did not harbor T790M mutation were enrolled. Toripalimab plus carboplatin and pemetrexed were administrated every three weeks for up to six cycles, followed by the maintenance of toripalimab and pemetrexed. The primary endpoint was objective-response rate (ORR). Integrated biomarker analysis of PD-L1 expression, tumor mutational burden (TMB), CD8 + tumor-infiltrating lymphocyte (TIL) density, whole-exome, and transcriptome sequencing on tumor biopsies were also conducted. Forty patients were enrolled with an overall ORR of 50.0% and disease-control rate (DCR) of 87.5%. The median progression free survival (PFS) and overall survival were 7.0 and 23.5 months, respectively. The most common treatment-related adverse effects were leukopenia, neutropenia, anemia, ALT/AST elevation, and nausea. Biomarker analysis showed that none of PD-L1 expression, TMB level, and CD8 + TIL density could serve as a predictive biomarker. Integrated analysis of whole-exome and transcriptome sequencing data revealed that patients with DSPP mutation had a decreased M2 macrophage infiltration and associated with longer PFS than those of wild type. Toripalimab plus chemotherapy showed a promising anti-tumor activity with acceptable safety profiles as the second-line setting in patients with EGFR-mutant NSCLC. DSPP mutation might serve as a potential biomarker for this combination. A phase-III trial to compare toripalimab versus placebo in combination with chemotherapy in this setting is ongoing (NCT03924050).
Conflict of interest statement
Honoraria to Dr. Caicun Zhou: Lilly, Roche, Boehringer Ingelheim, MSD, Hengrui Therapeutics, and QiLu Pharmaceutical; Consulting or advisory role: AmoyDx, Hengrui Therapeutics, Inovent, and QiLu Pharmaceutical. Other authors declared no potential conflicts of interest.
© 2021. The Author(s).
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