Efficacy and safety of amrubicin-based regimen used as first-line for extensive-disease small-cell lung cancer: A meta-analysis of randomized controlled trials.

ABSTRACT

BACKGROUND: Currently, amrubicin is used as first-line in the treatment of patients with small-cell lung cancer (SCLC). However, the effect of amrubicin-based treatment in extensive-disease (ED) SCLC remains controversial. Thus, we conducted a meta-analysis of randomized controlled trials (RCTs) to assess the efficacy and safety of amrubicin-based regimen in the treatment of patients with ED-SCLC. METHODS: RCTs published in PubMed, Web of Science, Embase, and ClinicalTrials.gov were systematically reviewed. Eligible studies were these that evaluated the efficacy and safety profiles of amrubicin-based regimen in ED-SCLC. Outcomes included progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and adverse events. Results were expressed with hazard ratio (HR) with 95% confidence intervals (CIs), and risk ratio (RR) with 95% CIs. RESULTS: Four RCTs involving a total of 740 patients met the inclusion criteria and were included in this meta-analysis. Amrubicin-based regimen was not associated with significantly prolonged PFS (HR = 1.07, 95% CI 0.90-1.30; P = 0.463) and OS (HR = 1.07, 95% CI 0.89-1.29; P = 0.443) in patients with ED-SCLC. However, it significantly improved ORR (RR = 1.14, 95% CI 1.04-1.25; P = 0.008). Subgroup analysis demonstrated that neither amrubicin alone nor in combination with cisplatin prolonged the PFS and OS, and only the combination therapy significantly increased ORR. The incidence of grade ≥3 adverse events was comparable between amrubicin-containing and other treatment groups (RR = 1.42, 95% CI 0.78-2.58; P = 0.248). However, amrubicin-based treatment induced a significantly higher incidence of febrile neutropenia (RR = 3.32, 95% CI 2.04-5.41; P < 0.001), anemia (RR = 1.44, 95% CI 1.06-1.97; P = 0.022), leukopenia (RR = 2.17, 95% CI 1.41-3.33; P < 0.001), neutropenia (RR = 1.33, 95% CI 1.04-1.70; P = 0.021), and interstitial lung disease (RR = 1.58, 95% CI 1.21-1.98; P < 0.001). CONCLUSION: Amrubicin-based regimen used as first-line had no survival benefits in patients with ED-SCLC. But it significantly improved ORR. Further well-conducted, large-scale trials are needed to validate these findings.