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

Background: 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.

Methods: 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.

Conclusions: 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.