Scientific Reports (Nov 2023)

Significance of micro-EGFR T790M mutations on EGFR-tyrosine kinase inhibitor efficacy in non-small cell lung cancer

  • Takeshi Masuda,
  • Satoru Miura,
  • Yuki Sato,
  • Motoko Tachihara,
  • Akihiro Bessho,
  • Atsushi Nakamura,
  • Taichi Miyawaki,
  • Kohei Yoshimine,
  • Masahide Mori,
  • Hideaki Shiraishi,
  • Kosuke Hamai,
  • Koji Haratani,
  • Sumiko Maeda,
  • Eriko Tabata,
  • Chiyoe Kitagawa,
  • Junko Tanizaki,
  • Takumi Imai,
  • Shohei Nogami,
  • Nobuyuki Yamamoto,
  • Kazuhiko Nakagawa,
  • Noboru Hattori

DOI
https://doi.org/10.1038/s41598-023-45337-3
Journal volume & issue
Vol. 13, no. 1
pp. 1 – 11

Abstract

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Abstract Small amounts of epidermal growth factor receptor (EGFR) T790M mutation (micro-T790M), which is detected using droplet digital PCR (ddPCR) but not conventional PCR, in formalin-fixed and paraffin-embedded (FFPE) samples have been investigated as a predictive factor for the efficacy of EGFR-tyrosine kinase inhibitors (TKIs). However, the predictive value of micro-T790M remains controversial, possibly owing to the failure to examine artificial T790M in FFPE specimens. Therefore, we examined the predictive value of micro-T790M in first-generation (1G), second-generation (2G), and third-generation (3G) EGFR-TKI efficacy using a new method to exclude FFPE-derived artificial mutations in our retrospective cohort. The primary objective was time to treatment failure (TTF) of 1G, 2G, and 3G EGFR-TKIs according to micro-T790M status. In total, 315 patients with EGFR-positive non-small cell lung cancer treated with 1G, 2G, and 3G EGFR-TKIs were included in this study. The proportion of patients positive for micro-T790M in the 1G, 2G, and 3G EGFR-TKI groups was 48.2%, 47.1%, and 47.6%, respectively. In the micro-T790M-positive group, the TTF was significantly longer in the 2G and 3G EGFR-TKI groups than in the 1G TKI group. No differences in the micro-T790M-negative group were observed. Micro-T790M status detected using ddPCR, eliminating false positives, may be a valuable predictor of EGFR-TKI efficacy.