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EGFR
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Interpretation 295
Tier 2
EGFR
Variants
EGFR T790M
Primary Sites
Stomach
Tumor Types
Adenocarcinoma
Squamous Cell Carcinoma
Interpretation

EGFR mutations have been reported in up to 5% of gastric cancers. The prognostic and predictive implications of EGFR mutations in gastric cancer have not been fully determined. Multiple clinical trials involving EGFR small molecule inhibitors and monoclonal antibodies are present, but limited and conflicting data preclude the therapeutic significance of EGFR mutations in gastric cancer. In NSCLC, an acquired T790M mutation in exon 20 is associated with resistance to some EGFR inhibitors. Third generation TKIs (e.g. osimertinib) have been shown to be effective in lung adenocarcinomas with the EGFR T790M mutation. A germline EGFR T790M mutation results in a rare lung cancer hereditary syndrome associated with increased risk in never-smokers. The presence of a germline EGFR T790M mutation also predicts for resistance to standard TKIs. The significance of EGFR T790M in gastric cancer should be considered in a relevant clinical context. Drug Resistance: Afatinib Erlotinib Gefitinib

Citations
  1. Liu Z, et al. Epidermal growth factor receptor mutation in gastric cancer. Pathology 2011;43(3):234-8
  2. Wong H, et al. Molecular targeted therapies in advanced gastric cancer: does tumor histology matter? Therap Adv Gastroenterol 2013;6(1):15-31
  3. Moutinho C, et al. Epidermal growth factor receptor structural alterations in gastric cancer. BMC Cancer 2008;8():10
  4. Dragovich T, et al. Anti-EGFR-Targeted Therapy for Esophageal and Gastric Cancers: An Evolving Concept. J Oncol 2009;2009():804108
  5. Ma C, et al. T790M and acquired resistance of EGFR TKI: a literature review of clinical reports. J Thorac Dis 2011;3(1):10-8
  6. Gazdar A, et al. Hereditary lung cancer syndrome targets never smokers with germline EGFR gene T790M mutations. J Thorac Oncol 2014;9(4):456-63
  7. Yu HA, et al. Germline EGFR T790M mutation found in multiple members of a familial cohort. J Thorac Oncol 2014;9(4):554-8
Last updated: 2018-04-18 14:23:32 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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