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

Purpose: To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in the treatment of desmoid tumors (DT). Patients and methods: In this investigator-initiated, double-blind, phase III 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 six 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 an HR of 0.05 (95% confidence interval, 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 in one (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 compared with placebo, with a favorable safety profile, for patients with progressive or symptomatic DTs. See related commentary by Dossa et al., p. 2127.