Distinct characteristics and clinical outcomes to predict the emergence of met amplification in patients with non-small cell lung cancer who developed resistance after treatment with epidermal growth factor receptor tyrosine kinase inhibitors

Beung Chul Ahn, Ji Hyun Lee, Min Hwan Kim, Kyoung Ho Pyo, Choong Kun Lee, Sun Min Lim, Hye Ryun Kim, Byoung Chul Cho, Min Hee Hong

Research output: Contribution to journalArticlepeer-review

Abstract

Objectives: Patients with epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) ultimately acquire resistance to EGFR tyrosine kinase inhibitors (TKIs) during treatment. In 5–22% of these patients, resistance is mediated by aberrant mesenchymal epithelial transition factor (MET) gene amplification. Here, we evaluated the emergence of MET amplification after EGFR-TKI treatment failure based on clinical parameters. Materials and Methods: We retrospectively analyzed 186 patients with advanced EGFR-mutant NSCLC for MET amplification status by in situ hybridization (ISH) assay after EGFR-TKI failure. We collected information including baseline patient characteristics, metastatic locations and generation, line, and progression-free survival (PFS) of EGFR-TKI used before MET evaluation. Multivariate logistic regression analysis was conducted to evaluate associations between MET amplification status and clinical variables. Results: Regarding baseline EGFR mutations, exon 19 deletion was predominant (57.5%), followed by L858R mutation (37.1%). The proportions of MET ISH assays performed after first/second-generation and third-generation TKI failure were 66.7% and 33.1%, respectively. The median PFS for the most recent EGFR-TKI treatment was shorter in MET amplification-positive patients than in MET amplification-negative patients (median PFS 7.0 vs. 10.4 months, p = 0.004). Multivariate logistic regression demonstrated that a history of smoking, short PFS on the most recent TKI, and less intracranial progression were associated with a high probability of MET amplification (all p < 0.05). Conclusions: Our results demonstrated the distinct clinical characteristics of patients with MET amplification-positive NSCLC after EGFR-TKI therapy. Our clinical prediction can aid physicians in selecting patients eligible for MET amplification screening and therapeutic targeting.

Original languageEnglish
Article number3096
JournalCancers
Volume13
Issue number12
DOIs
Publication statusPublished - 2021 Jun 2

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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