Role of the EGFR-KDD mutation as a possible mechanism of acquired resistance of non-small cell lung cancer to EGFR tyrosine kinase inhibitors: A case report

Epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) are currently considered as the standard therapy for patients with advanced non-small cell lung cancer (NSCLC) who have EGFR-activating mutations. However, despite an initially profound response to these drugs, these patients ultimately develop drug resistance. The most common resistance mechanism is the development of a secondary mutation in EGFR (T790M), although activation of the MNNG/HOS transforming gene (MET), amplification of the Erb-B2 receptor tyrosine kinase 2 gene and histological transformation to small cell lung cancer may also lead to resistance. In addition, there may be additional, rare mechanisms leading to resistance that remain unidentified. Mutations in the EGFR kinase domain duplication (EGFR-KDD) are rare, although they act as oncogenic drivers in NSCLC. To the best of our knowledge, all studies to date have reported EGFR-KDD as the primary mutation in NSCLC. The aim of the present study was to report the case of an EGFR-KDD mutation in a patient with NSCLC who developed acquired resistance to gefitinib, but responded well to afatinib. Therefore, EGFR-KDD mutation is an additional potential mechanism underlying the development of acquired resistance to EGFR-TKIs.