Abstract
BackgroundOsimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor–sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor–dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy.Case presentationWe report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective.ConclusionsDespite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor–mutant tumor.
Highlights
Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor–sensitizing and T790M resistance mutations
We report a rare case of a patient in whom epidermal growth factor receptor (EGFR) T790Mpositive adenocarcinoma transformed into large-cell neuroendocrine carcinoma (LCNEC) after osimertinib therapy
Histopathological and molecular analyses of transbronchial biopsy specimens from the right middle lobe revealed adenocarcinoma; the malignant epithelial cells were positive for carcinoembryonic antigen (CEA) and negative for synaptophysin (Fig. 2), and they harbored an exon 19 deletion mutation in EGFR
Summary
We report a case of a patient in whom EGFR T790Mpositive adenocarcinoma transformed into LCNEC after osimertinib therapy.
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