Liposomal Versus Conventional Doxorubicin as First-Line Therapy in Advanced Soft Tissue Sarcomas: Observational Multi-Institutional Cohort of 8.5-Year Experience

PURPOSE Doxorubicin (DOX) remains first-line therapy for advanced soft tissue sarcoma (STS) despite modest efficacy and cumulative cardiotoxicity. Pegylated liposomal doxorubicin (PLD) may reduce toxicity, but survival comparisons in STS are limited. We performed a multi-institutional retrospective cohort study comparing survival and adverse events in patients receiving first-line DOX versus PLD. METHODS This is a retrospective study of adults with unresectable or metastatic STS treated with first-line DOX or PLD at two cancer centers between 2016 and 2024. Overall survival (OS) and progression-free survival (PFS) were analyzed using the Kaplan-Meier method with log-rank testing and multivariable Cox proportional hazards models. Secondary outcomes, including objective response, treatment-related toxicities, hospitalizations, and dose modifications, were compared using Fisher's exact test. A post hoc sensitivity analysis was performed excluding angiosarcoma. RESULTS A total of 135 patients were included (91 DOX, 44 PLD). Baseline characteristics differed by histology, with angiosarcoma more frequent in the PLD group. Objective response rates were similar (DOX 8.8% v PLD 14.3%; P = .37), as were disease control rates (35.2% v 40.5%; P = .57). The median PFS was 2.1 months with DOX and 2.8 months with PLD, with no significant difference in multivariable analysis (hazard ratio [HR], 0.75 [95% CI, 0.50 to 1.12]; P = .15). The median OS was 12.4 months for DOX and 17.7 months for PLD, also not significantly different after adjustment (HR, 0.78 [95% CI, 0.47 to 1.30]; P = .34). Rates of hospitalization, cardiac toxicity, dose reductions, and grade III to IV toxicities did not differ significantly between groups. Sensitivity analyses excluding angiosarcoma (n = 119) similarly showed no significant differences in response or survival. CONCLUSION PLD and DOX demonstrated similar effectiveness with no statistically significant differences in tolerability detected as first-line therapy for advanced STS.