A meta-analysis of randomized controlled trials that compare standard doxorubicin with other first-line chemotherapies for advanced/metastatic soft tissue sarcomas

OBJECTIVE: The standard treatment for patients with advanced/metastatic soft tissue sarcomas (ASTS) is systemic chemotherapy with doxorubicin. A previous meta-analysis of 8 randomized controlled trials (RCTs) demonstrated the superiority of single-agent doxorubicin over doxorubicin-based combination chemotherapy for ASTS. However, meta-analyses of all RCTs that compare doxorubicin to other single-agent or combination regimens as first-line treatments for ASTS are lacking. We conducted a systematic review and meta-analysis to evaluate the efficacy and toxicity of current primary treatments for ASTS. METHODS: Eligible studies were RCTs of first-line chemotherapies for ASTS comparing doxorubicin alone to other single agents or to combination therapies (experimental arm). Data from studies reporting hazard ratios (HR) and 95% confidence intervals (CI) for overall survival (OS) and progression-free survival (PFS) were pooled. Other time-to-event endpoints were extracted from the studies based on Kaplan-Meier estimates, and pooled odds ratios (OR) and 95% CI were calculated. RESULTS: Twenty-seven eligible RCTs comprising 6156 patients were identified. Overall, the 1-year OS (OR 0.88, 95% CI 0.79–0.99, P = 0.03) was significantly improved in the experimental arm over the doxorubicin-only arm; however, there was no significant difference in 2-year OS (OR 0.87, 95% CI 0.73–1.03, P = 0.11) or OS (HR 0.97, 95% CI 0.91–1.03, P = 0.28) between the two groups. PFS and other time-to-event endpoints were not significantly different between the two treatment arms. While incidences of overall severe adverse events were not significantly different (OR 1.20, 95% CI 0.88–1.65, P = 0.26), severe nausea/vomiting was significantly more frequent in the experimental arm (OR 1.90, 95% CI 1.27–2.83, P = 0.002). CONCLUSION: The efficacies of doxorubicin-only and experimental arm regimens were similar, although toxicities were more frequent in the experimental arms. Hence, doxorubicin monotherapy remains suitable as a standard first-line regimen for ASTS.