Epidermal growth factor receptor-activating mutation(E746_T751>VP) in pancreatic ductal adenocarcinoma responds to erlotinib, followed by epidermal growth factor receptor resistance-mediating mutation (A647T): A case report and literature review

Girijesh Patel, Josiah Perry, Osama Abdul-Rahim, Arthur Frankel, Daniel Cameron, William Taylor, Rodney Rocconi, Laith Abushahin, Cindy Nelson, Ajay Singh, Moh'D Khushman

Research output: Contribution to journalReview articlepeer-review

3 Scopus citations

Abstract

Despite recent advances in treatment with multidrug chemotherapy regimens, outcomes of patients with advanced pancreatic ductal adenocarcinoma (PDAC) remain very poor. Treatment with targeted therapies has shown marginal benefits due to intrinsic or acquired resistance. Actionable mutations, while detected infrequently in patients with PDAC, are becoming increasingly used in personalized medicine. Here, we describe an epidermal growth factor receptor (EGFR)-activating mutation (E746_T751>VP) to erlotinib, a first-generation tyrosine kinase inhibitor (TKI), in a patient with metastatic PDAC. After an initial partial response to erlotinib for 12 months, the patient's disease progressed with emergence of the EGFR A647T mutation. Certainly, the patient also progressed after switching therapy to a third-generation EGFR TKI (osimertinib). This case illustrates the posttreatment evolution of EGFR A647T-mediated resistance to the first- and third-generation TKIs. To our knowledge, this is the first case to report the aforementioned activating and resistance-mediated mutations. In summary, genomic analysis performed in this patient with PDAC on the tumor biopsy and peripheral blood provided tools to understand mechanisms of response and resistance to targeted therapy with EFGR TKIs.

Original languageEnglish (US)
Pages (from-to)950-954
Number of pages5
JournalJournal of Cancer Research and Therapeutics
Volume16
Issue number4
DOIs
StatePublished - Jul 1 2020
Externally publishedYes

Keywords

  • A647T
  • E746_T751>VP mutation
  • epidermal growth factor receptor
  • erlotinib
  • osimertinib
  • pancreatic ductal adenocarcinoma
  • resistance

ASJC Scopus subject areas

  • Oncology
  • Radiology Nuclear Medicine and imaging

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