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

Yutao Liu1, Xuezhi Hao1, Xingsheng Hu1

  • 1Department of Medical Oncology, Beijing Key Laboratory of Clinical Study on Anticancer Molecular Targeted Drugs, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.

Thoracic Cancer
|February 8, 2018
PubMed

Insights

This study details a patient with EGFR-mutated lung adenocarcinoma who developed resistance to osimertinib due to MET amplification. Multiple resistance mechanisms highlight the need for combination therapies after osimertinib progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pharmacology

Background:

  • Osimertinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor targeting EGFR mutations.
  • Gefitinib is a first-generation EGFR inhibitor used in treating EGFR-mutated lung adenocarcinoma.

Observation:

  • A patient with EGFR-mutated lung adenocarcinoma developed resistance to osimertinib after initial gefitinib treatment.
  • The patient experienced rapid progression on osimertinib due to MET amplification, despite initial T790M mutation negativity.

Findings:

  • The study identified multiple and heterogeneous mechanisms of resistance to osimertinib.
  • MET amplification was a key factor in osimertinib resistance, leading to treatment failure.

Implications:

  • Combination strategies may be necessary to overcome osimertinib resistance in EGFR-mutated lung adenocarcinoma.
  • Understanding diverse resistance mechanisms is crucial for optimizing lung cancer treatment.
Keywords:
Epidermal growth factor receptor T790 mutationMET amplificationheterogeneityosimertinibresistance

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