Phase 3 Trial of Pegylated Liposomal Doxorubicin for Patients with Advanced and Refractory Desmoid Tumors

Summary

Purpose: To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in the treatment of desmoid tumors (DTs). Patients and methods: In this investigator-initiated, double-blind, phase 3 trial, we randomly assigned (in a 2:1 ratio) patients with advanced or refractory DTs to receive either PLD (50 mg/m² intravenously) or placebo every 4 weeks for 6 cycles. Crossover from placebo to PLD was permitted upon disease progression. The primary endpoint was progression-free survival (PFS). The secondary endpoints were objective response and safety. Results: From November 2020 to March 2023, a total of 73 patients were assigned to receive PLD (49 patients) or placebo (24 patients). With a median follow-up of 16.1 months, PLD had a significantly longer PFS over placebo (not reached vs. 4.3 months), with a hazard ratio (HR) of 0.05 (95% CI, 0.01-0.17; P<0.001). The 2-year PFS rates were 90.4% with the PLD group and 19.6% with placebo. PFS benefit favored PLD across most prespecified subgroups. The confirmed objective response was observed in 19 (40.4%) patients in the PLD group and 1 (4.3%) in the placebo group (P=0.002). Common grade 3 or higher adverse events with PLD included neutrophil count decreased (10.6%), mucositis oral (6.4%), and white-cell decreased (4.3%). Significant between-group differences in certain patient-reported toxicities were observed (P<0.05). Conclusions: PLD significantly prolonged PFS and induced durable responses than placebo, with a favorable safety profile, for patients with progressive or symptomatic desmoid tumors.