Abstract
Advances in molecular biology have positioned epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) as highly effective therapies for patients with EGFR-mutant carcinomas. However, the inevitable emergence of acquired resistance significantly limits their long-term efficacy. Among resistance mechanisms, the transformation of lung adenocarcinoma to small cell lung cancer (SCLC) following EGFR-TKIs therapy is an uncommon but clinically important phenomenon contributing to treatment failure. We present a case of SCLC transformation in a patient with EGFR-mutant lung adenocarcinoma after 8 months of first-line osimertinib therapy. Following 4 cycles of etoposide combined with lobaplatin chemotherapy, adenocarcinoma cells regained predominance, illustrating a dynamic histological shift between adenocarcinoma and SCLC phenotypes. Subsequent treatment with 2 cycles of chemotherapy plus osimertinib resulted in disease stabilization. However, multiple brain metastases were identified 3 months after completing 6 cycles of chemotherapy. This case underscores the bidirectional histological plasticity between lung adenocarcinoma and SCLC during treatment and highlights the critical importance of repeated biopsies for guiding management strategies in the context of resistance. We also provide a comprehensive review of the clinical manifestations, underlying mechanisms, predictive biomarkers, and therapeutic approaches for SCLC transformation.