A case of evolving resistance in EGFR-mutant lung adenocarcinoma with subsequent small cell transformation: A diagnostic and therapeutic challenge

This report details the complex clinical course of a 57-year-old female with metastatic lung adenocarcinoma harboring an EGFR exon 19 deletion. Diagnosed in October 2022, she initially responded to first-line gefitinib but developed intolerable cutaneous toxicity. After switching to afatinib and later osimertinib upon progression, a repeat biopsy in June 2024 confirmed histologic transformation to small cell carcinoma (Ki-67: 90-95%), a recognized resistance mechanism. Management successfully pivoted to platinum-etoposide chemotherapy, achieving a good initial response. Subsequent disease progression was complicated by severe infections and cytopenias, necessitating multiple salvage regimens. This case underscores the imperative of tissue re-biopsy at progression to guide therapy and highlights the therapeutic challenges and morbidity associated with small cell transformation in EGFR-mutant NSCLC.