To investigate the efficacy of irinotecan-based (IP) and etoposide-based (EP) platinum combinations, and of single-agent chemotherapy, for treatment of extensive-disease small cell lung cancer (ED-SCLC), we performed a large-scale, retrospective, nationwide, cohort study. The population data were extracted from the Health Insurance Review and Assessment Service of Korea database from January 1, 2008, to November 30, 2016. A total of 9,994 patients were allocated to ED-SCLC and analyzed in this study. The primary objectives were to evaluate the survival outcomes of systemic first-line treatments for ED-SCLC. For first-line treatment, patients who received IP showed a better time to first subsequent therapy (TFST) of 8.9 months (95% confidence interval [CI], 8.50–9.40) than those who received EP, who had a TFST of 6.8 months (95% CI, 6.77–6.97, P