Frequency of EGFR T790M mutation and multimutational profiles of rebiopsy samples from non-small cell lung cancer developing acquired resistance to EGFR tyrosine kinase inhibitors in Japanese patients. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Ko, Ryo; Kenmotsu, Hirotsugu; Serizawa, Masakuni; Koh, Yasuhiro; Wakuda, Kazushige; Ono, Akira; Taira, Tetsuhiko; Naito, Tateaki; Murakami, Haruyasu; Isaka, Mitsuhiro; Endo, Masahiro; Nakajima, Takashi; Ohde, Yasuhisa; Yamamoto, Nobuyuki; Takahashi, Kazuhisa; Takahashi, Toshiaki
• Is Part Of: BMC cancer. Volume 16:Issue 1(2016)
• Page Start: 1
• Page End: 8
• Publication Date: 2016-12
• Subjects: Non-small cell lung cancer -- Epidermal growth factor receptor mutation -- Rebiopsy -- T790M mutation; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s12885-016-2902-0
• Languages: English
• ISSNs: 1471-2407

Abstract

Abstract Background The majority of non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR ) mutation eventually develop resistance to EGFR tyrosine kinase inhibitors (TKIs). Minimal information exists regarding genetic alterations in rebiopsy samples from Asian NSCLC patients who develop acquired resistance to EGFR-TKIs. Methods We retrospectively reviewed the medical records of patients with NSCLC harboringEGFR mutations who had undergone rebiopsies after developing acquired resistance to EGFR-TKIs. We analyzed 27 practicable samples using a tumor genotyping panel to assess 23 hot-spot sites of genetic alterations in nine genes (EGFR, KRAS, BRAF, PIK3CA, NRAS, MEK1, AKT1, PTEN, andHER2 ), gene copy number ofEGFR, MET, PIK3CA, FGFR1, andFGFR2, andALK, ROS1, andRET fusions. Additionally, 34 samples were analyzed by commercially availableEGFR mutation tests. Results Sixty-one patients underwent rebiopsy. Twenty-seven samples were analyzed using our tumor genotyping panel, and 34 samples were analyzed forEGFR mutations only by commercial clinical laboratories. Twenty-one patients (34%) hadEGFR T790M mutation. Using our tumor genotyping panel, MET gene copy number gain was observed in two of 27 (7%) samples. Twenty patients received continuous treatment with EGFR-TKIs even after disease progression, and 11 of these patients had T790M mutation in rebiopsy samples. In contrast, only 10 of 41 patients who finished EGFR-TKI treatment at disease progression had T790M mutation. The frequency of T790M mutation in patients who received continuous treatment with EGFR-TKIs after disease progression was significantly higher than that in patients who finished EGFR-TKI treatment at disease progression (55% versus 24%, p = 0.018). Conclusions The frequency of T790M mutation in this study was lower than that in previous reports examining western patients. These results suggest that continuous treatment with EGFR-TKI after disease progression may enhance the frequency ofEGFR T790M mutation in rebiopsy samples.