Response to Brigatinib Targeted Therapy in Non-Small Cell Lung Cancer Harboring Epidermal Growth Factor Receptor Exon 19 Deletion, T790M, and cis-C797S Triple Mutations: A Case Report

Zi Wei Chen, Gigin Lin, Hsuan Jen Shih*, Chiao En Wu*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

Abstract

Epidermal growth factor receptor (EGFR) triple mutations with exon 19 deletion (del19), T790M, and cis-C797S (del19/T790M/cis-C797S mutations) frequently occur in patients with non-small cell lung cancer (NSCLC), while progression to frontline EGFR-tyrosine kinase inhibitors (TKIs) and osimertinib was resistant to all clinically available EGFR-TKIs. Brigatinib monotherapy may be a potential treatment for NSCLC harboring del19/T790M/cis-C797S mutations based on preclinical studies; however, no clinical report has evaluated its efficacy on EGFR del19/T790M/cis-C797S mutations. Herein, we present a case of a female patient with EGFR del19-mutated NSCLC treated with afatinib followed by osimertinib due to acquired T790M mutation. The EGFR del19/T790M/cis-C797S mutations were detected following osimertinib treatment. Complete response of skull metastasis was confirmed after brigatinib treatment (90 mg daily). Unfortunately, she experienced intolerable adverse events; therefore, brigatinib was discontinued after three-month usage. This report provides the first reported evidence for the use of brigatinib monotherapy in patients with NSCLC harboring EGFR del19/T790M/cis-C797S mutations after progression to previous EGFR-TKIs.

Original languageEnglish
Article number602
JournalInternational Journal of Molecular Sciences
Volume24
Issue number1
DOIs
StatePublished - 29 12 2022

Bibliographical note

Publisher Copyright:
© 2022 by the authors.

Keywords

  • EGFR triple mutation
  • EGFR-tyrosine kinase inhibitors resistance
  • NSCLC
  • T790M-cis-C797S
  • brigatinib
  • osimertinib resistance
  • Aniline Compounds/therapeutic use
  • Exons
  • Humans
  • Lung Neoplasms/drug therapy
  • Carcinoma, Non-Small-Cell Lung/drug therapy
  • Drug Resistance, Neoplasm/genetics
  • Female
  • Mutation
  • Protein Kinase Inhibitors/pharmacology
  • ErbB Receptors/metabolism

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