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Background: Extensive-disease small-cell lung cancer (ED-SCLC) has been known to be rapid progression and relapse, despite highly sensitive to chemotherapy. Amrubicin (AMR), a third-generation synthetic anthracycline, was accepted as a feasible alternative compared with the standard first-line chemotherapy for previously untreated ED-SCLC. While, the efficacies of these amrubicin-based regimens are unsatisfactory. Aim: Our meta-analysis was performed to assess the efficacy and toxicity of first-line therapy comparing AMR and chemotherapy in patients with ED-SCLC. Methods: Electronic databases were searched for eligible trials updated on November 2018. Randomized-controlled trials assessing the efficacy and safety of AMR in ED-SCLC were included, of which the interested results were objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and adverse events (AEs). Results: A total of 6 randomized controlled trials were included in this analysis. There are no significant differences in OS (OR=1.03, 95% CI=0.66–1.60, P=0.91), PFS (OR=1.2, 95% CI=10.77–1.88, P=0.41) or ORR (OR=1.31, 95% CI=0.90–1.92, P=0.16) with AMR (OR=0.90, 95% CI=0.76–1.05, P=0.17). The most common treatment-related AEs in the AMR group are leukopenia (OR=3.13, 95% CI=1.22–7.99, P=0.02) and neutropenia (OR=3.25, 95% CI=1.38–7.65, P=0.007). Fatigue, anemia, nausea, vomiting, diarrhea the difference between the two groups had no statistical significance. Conclusion: The results of our analysis indicated that AMR therapy demonstrated non-inferiority to the standard first-line chemotherapy for previously untreated ED-SCLC. Whether it can be accepted as an alternative regimen to the standard first-line chemotherapy is still warranted. [ABSTRACT FROM AUTHOR]