Molecular correlation of response to pyrotinib in advanced NSCLC with HER2 mutation: biomarker analysis from two phase II trials

Experimental Hematology & Oncology

Research

Qiming Wang¹  Jianhua Chen²  Shuo Yang³  Xinyu Liu³  Shiqi Mao³  Tao Jiang³  Shengxiang Ren³  Fengying Wu³  Yan Wang³  Caicun Zhou³  Guanghui Gao³  Yiping Zhang⁴  Ying Yang⁵  Jiao Zhang⁵  Xiaoyu Zhu⁶  Xiang Lin⁶  Xingya Li⁷ 

[1] Department of Internal Medicine, Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, 450008, Zhengzhou, China;Department of Medical Oncology, Cancer Hospital of Central South University, 410006, Changsha, China;Department of Medical Oncology, Shanghai Pulmonary Hospital, Cancer Institute, Tongji University School of Medicine, 200433, Shanghai, China;Department of Thoracic Oncology, Zhejiang Cancer Hospital, 310000, Hangzhou, China;Genecast Biotechnology Co., Ltd, 214104, Wuxi, China;Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China;Second Ward of Oncology, The First Affiliated Hospital of Zhengzhou University, 450000, Zhengzhou, China;

关键词: Non-small cell lung cancer;    HER2;    pyrotinib ;    ctDNA;   

DOI  :  10.1186/s40164-023-00417-y

 received in 2022-10-26, accepted in 2023-05-18,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundNon-small cell lung cancer (NSCLC) with HER2 mutation has entered into the era of targeted therapy. However, both anti-HER2 antibody–drug conjugates (ADCs) and tyrosine kinase inhibitors (TKIs) showed moderate objective response rate (ORR) and median progression-free survival (PFS). The aim of this study was to investigate the molecular features of responders to pyrotinib in advanced NSCLC with HER2 mutation.MethodsPatients from our two previous phase II trials were pooled analyzed. Their circulating tumor DNA (ctDNA) were detected by next-generation sequencing (NGS) panels, and the correlation with the efficacy of pyrotinib was investigated.ResultsThis pooled analysis included 75 patients, and 50 of them with baseline plasma samples were finally enrolled with a median age of 57 years old. The overall ORR and median PFS were 28% and 7.0 months respectively. Biomarker analysis showed that 5 patients were ctDNA nonshedding. Patients with TP53 wild type were significantly associated with higher disease control rate (97.1%vs. 68.8%, p = 0.010), PFS (median 8.4 vs. 2.8 months, p = 0.001) and overall survival (OS, median 26.7 vs. 10.4 months, p < 0.001) than those with mutations. ctDNA of nonshedding and clearance exhibited significantly longer PFS (median: 10.2 vs. 9.8 vs. 5.6 months, p = 0.036) and a trend of longer OS (median: 35.3 vs. 18.1 vs. 14.6 months, p = 0.357) than those not.ConclusionPatients with TP53 wild type, ctDNA nonshedding, or clearance showed superior efficacy of pyrotinib in patients with HER2-mutated advanced NSCLC, which might be helpful to guide the utility of pyrotinib in clinical setting.Trial registration: The patients were from two registered clinical trials (ClinicalTrials.gov: NCT02535507, NCT02834936).

【 授权许可】

CC BY   
© The Author(s) 2023

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