Open AccessReal‐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
Author(s) -
Lei Lei,
Wang Wenxian,
Zhu Youcai,
Li Jinluan,
Fang Yong,
Wang Hong,
Zhuang Wu,
Zhang Yinbin,
Wang Liping,
Fang Meiyu,
Xu Chunwei,
Wang Xiaojia,
Lv Tangfeng,
Song Yong
Publication year - 2020
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.2652
Subject(s) - medicine , t790m , oncology , lung cancer , mutation , epidermal growth factor receptor , cancer , gastroenterology , gefitinib , biology , gene , genetics
The response to icotinib in advanced non‐small cell lung cancers (NSCLC) with EGFR uncommon mutation ( EGFR um) is unclear. Here we reported the efficacy and potential resistance mechanism of icotinib in Chinese EGFR um NSCLC patients. Between July 2013 and November 2016, 3117 NSCLC patients were screened for EGFR um 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 ( EGFR cm) and single‐pattern have better PFS than complex‐pattern without EGFR cm (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 EGFR cm group. S768I mutation carriers may not benefit from icotinib. Acquired T790M mutation was common in icotinib‐resistant EGFR um NSCLC patients.