Real-world efficacy and potential mechanism of resistance of icotinib in Asian advanced non-small cell lung cancer with EGFR uncommon mutations: A multi-center study.

Abstract

The response to icotinib in advanced non-small cell lung cancers (NSCLC) with EGFR uncommon mutation (EGFRum) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFRum NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFRum in a multi-center study in China. Circulating tumor DNA (ctDNA) was detected and analyzed using next-generation sequencing (NGS) after progression from icotinib. The efficacy, safety and the potential resistance mechanism of icotinib were explored. After a median follow-up of 6.2 months, 69 patients (70.41%) developed disease progression, the objective rate (ORR) and disease control rate (DCR) were 13.27% and 29.59% respectively, and the median progression-free survival (PFS) was 5.5 months (95% CI: 1.2-13.0 months). Both complex-pattern with EGFR classical mutations (EGFRcm) and single-pattern have better PFS than complex-pattern without EGFRcm (median PFS was 7.2 (95% CI: 4.65-9.75), 5.2 (95% CI: 3.24-7.16) and 3.2 (95% CI: 2.97-3.44) months, respectively, P < .05); patients harboring S768I mutation had the worst PFS than others (2.0 months, P < .05). Diarrhea was the most frequent side effect (42.9%). Forty-eight (69.6%) patients developed drug resistance after 3.0 months and 81.2% of them acquired T790M mutation. Better response was observed in complex-pattern with the EGFRcm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib-resistant EGFRum NSCLC patients.

• Authors: Lei Lei, Wen-Xian Wang, You-Cai Zhu, Jin-Luan Li, Yong Fang, Hong Wang, Wu Zhuang, Yin-Bin Zhang, Li-Ping Wang, Mei-Yu Fang, Chun-Wei Xu, Xiao-Jia Wang, Tang-Feng Lv, Yong Song
• Journal: Cancer medicine (Cancer Med) Vol. 9 Issue 1 Pg. 12-18 (01 2020) ISSN: 2045-7634 [Electronic] United States
• PMID: 31692291 (Publication Type: Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Circulating Tumor DNA
• Crown Ethers
• Protein Kinase Inhibitors
• Quinazolines
• icotinib
• EGFR protein, human
• ErbB Receptors

Topics

• Aged
• Asian People (genetics)
• Carcinoma, Non-Small-Cell Lung (blood, drug therapy, genetics, mortality)
• China (epidemiology)
• Circulating Tumor DNA (blood, genetics)
• Crown Ethers (pharmacology, therapeutic use)
• DNA Mutational Analysis
• Disease Progression
• Drug Resistance, Neoplasm (genetics)
• ErbB Receptors (antagonists & inhibitors, genetics)
• Female
• Follow-Up Studies
• High-Throughput Nucleotide Sequencing
• Humans
• Lung Neoplasms (blood, drug therapy, genetics, mortality)
• Male
• Middle Aged
• Mutation (drug effects)
• Progression-Free Survival
• Protein Kinase Inhibitors (pharmacology, therapeutic use)
• Quinazolines (pharmacology, therapeutic use)
• Retrospective Studies