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

Abstract

To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in the treatment of desmoid tumors (DTs). 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. 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). PLD significantly prolonged PFS and induced durable responses than placebo, with a favorable safety profile, for patients with progressive or symptomatic desmoid tumors.