Comprehensive analysis of treatment modes and clinical outcomes of small cell lung cancer transformed from epidermal growth factor receptor mutant lung adenocarcinoma

• Main Authors: Shouzheng Wang, Tongji Xie, Xuezhi Hao, Yan Wang, Xingsheng Hu, Lin Wang, Yan Li, Junling Li, Puyuan Xing
• Format: Article
• Language: English
• Published: Wiley 2021-10-01
• Series: Thoracic Cancer
• Subjects: anti‐angiogenesis; epidermal growth factor receptor mutation; lung adenocarcinoma; small cell histological transformation; tyrosine kinase inhibitors
• Online Access: https://doi.org/10.1111/1759-7714.14144

Abstract Background Transformation to small cell lung cancer (SCLC) is a resistance mechanism of epidermal growth factor receptor (EGFR) mutant lung adenocarcinoma (LADC) patients treated with EGFR tyrosine kinase inhibitors (TKIs). Here, we describe the clinical characteristics and prognosis of these patients and explore the treatment modes after transformation. Methods EGFR‐mutant LADC patients with SCLC transformation were retrospectively included in the study. Demographic and clinical data were collected. Survival outcomes and corresponding influential factors were analyzed. Results Twenty‐nine patients were included in the study. The median progression‐free survival (PFS) of patients who received first‐line EGFR‐TKIs was 13.1 months. The median time to SCLC transformation was 27.5 months. After transformation, the objective response rates of patients who received first‐line chemotherapy with or without EGFR‐TKIs were 43.8% and 37.5%, respectively. The median PFS of patients reveiving chemotherapy with EGFR‐TKIs was significantly longer than that of patients receiving chemotherapy without EGFR‐TKIs (5.2 vs. 3.0 months; HR, 0.19; 95% CI: 0.05–0.72; p = 0.014). However, there was no significant difference in median overall survival (OS) between patients who received chemotherapy with or without EGFR‐TKIs (14.8 vs. 13.0 months; p = 0.474). In the multivariate Cox proportional hazards regression analysis, both anti‐angiogenic treatment (HR, 0.04; 95% CI: 0.01–0.29; p = 0.001) and local radiotherapy (HR, 0.28; 95% CI: 0.08–0.97; p = 0.044) were significantly associated with better patient OS after transformation. Conclusions Compared with chemotherapy alone, the combination of chemotherapy and EGFR‐TKIs as first‐line treatment after SCLC transformation can benefit patients in PFS but not in OS. However, anti‐angiogenic therapies and local radiotherapy can significantly prolong OS after transformation.