Liposomal vs conventional doxorubicin as first-line therapy in advanced soft tissue sarcomas: A tertiary US center’s 8.5-year experience.

Abstract

e23533 Background: Patients with advanced soft tissue sarcoma (STS) are commonly treated with either conventional doxorubicin (dox) or liposomal doxorubicin (PLD), yet direct comparisons of their efficacy, survival, and toxicity differences are limited. This retrospective study evaluates the differences in real-world outcomes among patients treated with both regimens and compares progression-free/overall survival (PFS/OS), disease control rate (DCR), and toxicities. Methods: We conducted a retrospective analysis of 102 patients with advanced STS treated at University of Pennsylvania Health System sites between January 2016 and August 2024, with either dox or PLD. Patients receiving combination or peri-operative treatment were excluded. Baseline characteristics were compared using Fisher’s exact tests. OS was assessed using Kaplan-Meier analysis and log-rank tests. Cox proportional hazards models estimated hazard ratios (HRs) for OS, adjusting for covariates age, ECOG performance status (PS), and metastatic pattern. Interaction terms were included to evaluate effect modification. DCR and grade 3-4 toxicities were compared using Fisher’s exact tests, with logistic regression estimating adjusted odds ratios. The study had the power of 73% to detect differences in OS based on prior published data. Stata 18 and R v4.4.1 were used for the analysis. Results: Patients (total n=102) treated with PLD (n=35) were older (mean age 70.3 vs. 61.1 years) and less likely to have primary tumor arising from trunk/extremities (26% vs.42%) than those treated with dox (n=67). No significant differences were observed in sex, ECOG PS, metastatic pattern (none vs lung-only vs. other), or overall comorbidity burden. Median OS was 17.7 months for PLD and 12.3 months for dox (unadjusted HR=0.83, 95% CI: 0.51-1.37, p= 0.48 and adjusted HR 1.00 95%CI 0.59-1.70). Median PFS was 2.6 months for PLD and 2.14 months for dox (unadjusted HR=0.76, 95% CI: 0.48-1.17, p= 0.21 and adjusted HR 0.78 95% CI 0.50-1.23 p=0.29). ECOG PS was an important prognostic factor: patients with ECOG 0-1 had a median OS of 15.3 months, versus 5.24 months for ECOG ≥2 (HR 2.17 CI 95% 1.24-3.78 p=0.006). The interaction between ECOG and metastatic pattern was significant; patients with ECOG PS 2-3 and non-lung-only metastases had an HR for death of 9.25 (95% CI: 1.53-55.8, p=0.02). DCR was similar between groups (40% PLD vs. 39% dox). There were no significant differences in the incidence of grade 3-4 toxicities (p=0.09). Conclusions: In this retrospective cohort of patients with advanced STS, patients receiving dox vs. PLD did not experience significantly different OS, DCR or toxicities. ECOG PS and metastatic pattern jointly influenced survival outcomes, underscoring their importance in prognosis.