Outcome of patients with lung adenocarcinoma with transformation to small-cell lung cancer following tyrosine kinase inhibitors treatment: A systematic review and pooled analysis

Background: Lung adenocarcinoma can transform to small-cell lung cancer (SCLC) when resistance to tyrosine kinase inhibitors (TKIs) develops. This phenomenon has repeatedly been described in several case reports and small patient series. The characteristics and treatment outcomes of this population, however, have not been comprehensively reported. Methods: We performed a systematic review of the published literature to obtain explorative information on the clinical and pathological features and prognosis of the reported cases. Results: Twenty-five eligible publications were identified, contributing to 39 patients. The median time from initial diagnosis of lung adenocarcinoma to the transformation to SCLC (ttSCLC) was 19 months (range 1-61 months). The median survival after SCLC diagnosis was 6 months. Female gender was significantly associated with longer ttSCLC at the multivariable analysis. Smoking status seemed to be associated with worse prognosis after the diagnosis of SCLC. Conclusion: In this series of published cases, the transformation to a SCLC phenotype after an initial diagnosis of lung adenocarcinoma following TKI therapy appeared to be a late phenomenon. The prognosis after SCLC diagnosis is poor and current treatment strategies derived from primary SCLC seem to be largely inefficacious. New therapies are needed in the management of transformed SCLC. (C) 2017 Elsevier Ltd. All rights reserved.