Open AccessEpidermal 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
Author(s) -
Girijesh Kumar Patel,
Josiah B Perry,
Osama Abdul-Rahim,
Arthur E. Frankel,
Daniel Cameron,
William R. Taylor,
Rodney P. Rocconi,
Laith Abushahin,
Cindy Nelson,
Ajay P. Singh,
Moh’d Khushman
Publication year - 2020
Publication title -
journal of cancer research and therapeutics/journal of cancer research and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 39
eISSN - 0973-1482
pISSN - 1998-4138
DOI - 10.4103/jcrt.jcrt_729_18
Subject(s) - erlotinib , epidermal growth factor receptor , medicine , adenocarcinoma , epidermal growth factor , oncology , cancer research , pancreatic intraepithelial neoplasia , erlotinib hydrochloride , pancreatic cancer , cancer , pancreatic ductal adenocarcinoma , receptor
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.