Author:
Mao Shiqi,Yang Shuo,Liu Xinyu,Li Xingya,Wang Qiming,Zhang Yiping,Chen Jianhua,Wang Yan,Gao Guanghui,Wu Fengying,Jiang Tao,Zhang Jiao,Yang Ying,Lin Xiang,Zhu Xiaoyu,Zhou Caicun,Ren Shengxiang
Abstract
Abstract
Background
Non-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.
Methods
Patients 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.
Results
This 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.
Conclusion
Patients 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).
Funder
National Natural Science Foundation of China
Shanghai Innovative Collaboration Project
Shanghai Shenkang Hospital Development Center
Science and Technology Commission of Shanghai Municipality
Clinical Research foundation of Shanghai Pulmonary Hospital
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Oncology,Hematology