Sequential occurrence of T790M mutation and small cell lung cancer transformation in EGFR-positive lung adenocarcinoma: A case report

The emergence of secondary drug resistance when treating epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) using EGFR-tyrosine kinase inhibitors (EGFR-TKIs), seriously affects the therapeutic efficacy and survival of patients. Here, we report a case of advanced NSCLC focusing on the application of multiple biopsy modalities to reveal the development of multiple resistance mechanisms during targeted therapies.A 54-year-old male patient presented with EGFR 19Del-mutated advanced lung adenocarcinoma, and exhibited the development of a T790M mutation during initial TKI treatment. Following 3 mo of Osimertinib treatment, a mixed response was observed. Tissue biopsy of the progressive lesion showed transformation to small cell lung cancer (SCLC) harboring RB1 and TP53 mutations, with loss of the original T790M mutation. A standard chemotherapy regimen with Anlotinib for SCLC was administered. Repeat biopsy revealed adenocarcinoma combined with SCLC after tumor progression. The patient's overall survival was 24 mo.Multiple biopsy modalities can reveal the development of multiple resistance mechanisms which help with treatment decision-making. Comprehensive treatment regimens according to the drug resistance mechanism significantly improved the prognosis of such patients.