Histologic Transformation in an EGFR-Mutant Lung Cancer in a Filipino Patient treated with Afatinib: A Case Report and Review of Literature

We report a case of a 64-year-old Filipino male who initially presented with chronic cough, easy fatigability, and weight loss. Work-ups lead to a diagnosis of lung adenocarcinoma with epidermal growth factor receptor (EGFR) exon 19 deletion. Patient was placed on targeted therapy with Afatinib. He was able to complete 17 months of targeted therapy with relatively stable disease before experiencing recurrence of easy fatigability. Work-ups then lead to a diagnosis of a high-grade neuroendocrine tumor consistent with small cell lung carcinoma (SCLC). Afatinib was then discontinued and the patient was started on Carboplatin and Etoposide. However, after only one cycle, the patient’s symptoms progressed and the patient eventually expired. Histological transformation of EGFR-mutant adenocarcinoma to SCLC as a mechanism of resistance to targeted therapy has been documented in literature since 2006. However, to our knowledge, this is the first fully-documented case of histologic transformation occurring in a Filipino patient. As molecular targeted therapy and immunotherapy become standard-of-care in our country, it is of paramount importance that clinicians and pathologists are aware of the various mechanisms of resistance that can occur as a result of these treatments.