Toripalimab plus chemotherapy as second-line treatment in previously EGFR-TKI treated patients with EGFR-mutant-advanced NSCLC: a multicenter phase-II trial.
Tao JiangPingyang WangJie ZhangYanqiu ZhaoJianying ZhouYun FanYongqian ShuXiaoqing LiuHelong ZhangJianxing HeGuanghui GaoXiaoqian MuZhang BaoYanjun XuRenhua GuoHong WangLin DengNingqiang MaYalei ZhangHui FengSheng YaoJiarui WuLuonan ChenCaicun ZhouShengxiang RenPublished in: Signal transduction and targeted therapy (2021)
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).
Keyphrases
- small cell lung cancer
- phase iii
- epidermal growth factor receptor
- advanced non small cell lung cancer
- tyrosine kinase
- wild type
- single cell
- open label
- free survival
- brain metastases
- chronic kidney disease
- clinical trial
- end stage renal disease
- gene expression
- newly diagnosed
- chemotherapy induced
- adipose tissue
- randomized controlled trial
- phase ii
- study protocol
- squamous cell carcinoma
- replacement therapy
- combination therapy
- machine learning
- peripheral blood
- copy number
- drug induced
- ejection fraction
- artificial intelligence
- data analysis
- electronic health record
- phase ii study