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Heterogeneity-based, multiple mechanisms in the resistance to osimertinib (AZD9291): A case report.

Yutao LiuXuezhi HaoXingsheng HuJunling LiYan WangHongyu WangPuyuan XingWeihua LiJianming YingXiaohong HanYuan-Kai Shi
Published in: Thoracic cancer (2018)
Osimertinib is a novel, irreversible, mutant-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations and the EGFR T790 mutation. Here, we report a woman with EGFR-mutated lung adenocarcinoma who, after 23-month treatment with gefitinib, developed the EGFR T790M mutation, which converted the T790M status from positive to negative before osimertinib treatment and developed MET amplification, leading to rapid progression on osimertinib in two months. Subsequent treatment with crizotinib and c-Met inhibitor plus gefitinib also failed to improve the clinical outcome, suggesting the potential existence of another resistance mechanism. Our findings revealed the underlying multiple and heterogeneous mechanisms in resistance to osimertinib, suggesting combination strategies should be considered post-osimertinib progression.
Keyphrases
  • epidermal growth factor receptor
  • tyrosine kinase
  • advanced non small cell lung cancer
  • small cell lung cancer
  • single cell
  • combination therapy
  • drug delivery
  • climate change
  • quantum dots