Pegylated Liposomal Doxorubicin Improves Progression-Free Survival in Patients With Progressive Desmoid Tumors

Clinical Summary:

• Design/Population: This randomized, double-blind, phase 3 trial evaluated pegylated liposomal doxorubicin versus placebo in patients with progressive or symptomatic advanced desmoid tumors.

• Key Outcomes: Pegylated liposomal doxorubicin significantly improved progression-free survival and objective response rate compared with placebo while demonstrating a manageable safety profile.

• Clinical Relevance: These findings support pegylated liposomal doxorubicin as an effective systemic treatment option for patients with progressive or symptomatic desmoid tumors.

Results from a phase 3 trial demonstrated that pegylated liposomal doxorubicin significantly improved progression-free survival (PFS) and objective response rate (ORR) compared with placebo in patients with progressive or symptomatic desmoid tumors, supporting the agent as a potential new systemic treatment option.

“Although not malignant, [desmoid tumors] are often locally aggressive and may present with severe functional impairments, disfigurement, and pain, resulting in a substantial clinical burden,” stated Huaiyuan Xu, MD, Sun Yat-Sen University Cancer Center, Guangzhou, China, and coauthors. “Even after complete surgical resection, the risk of recurrence remains high, presenting a considerable challenge for disease management.”  

In this double-blind, placebo-controlled trial, 70 patients with symptomatic, unresectable, or potentially disabling desmoid tumors who experienced radiographic disease progression within 6 months of enrollment were randomized 2:1 to receive either 50 mg/m² of pegylated liposomal doxorubicin (n = 49) or placebo (n = 24) every 4 weeks for up to 6 cycles. Patients assigned to placebo were permitted to cross over to pegylated liposomal doxorubicin after disease progression. The primary end point was investigator-assessed PFS. Key secondary end points included ORR and safety.

At a median follow-up of 16.1 months, median PFS was not reached in the pegylated liposomal doxorubicin arm and was 4.3 months in the placebo arm (hazard ratio [HR], 0.05; 95% confidence interval [CI], 0.01 to 0.17; P < .001). Estimated 1-year PFS rates were 95.7% and 19.6%, respectively, while estimated 2-year PFS rates were 90.4% and 19.6%.

The confirmed ORR was 40.4% with pegylated liposomal doxorubicin compared with 4.3% with placebo (P = .002). Most patients who responded to pegylated liposomal doxorubicin remained in response at the time of data cutoff.

Any-grade adverse events occurred in 91.5% of patients receiving pegylated liposomal doxorubicin and 36.4% of those receiving placebo. Grade ≥3 adverse events occurred in 14.9% of patients treated with pegylated liposomal doxorubicin. The most common grade ≥3 adverse events included decreased neutrophil count (10.6%), oral mucositis (6.4%), and decreased white blood cell count (4.3%). Two patients required dose reductions because of adverse events, and no patients discontinued treatment because of toxicity.

“Given its efficacy, safety, and accessibility, [pegylated liposomal doxorubicin] could be considered a preferred treatment option with a favorable benefit/risk balance for patients with advanced [desmoid tumors],” concluded Dr Xu and coauthors. 

Source:

Xu H, Hu J, Zhang Y, et al. Phase III trial of pegylated liposomal doxorubicin for patients with advanced and refractory desmoid tumors. Clin Cancer Res. Published online June 1, 2026. doi: 10.1158/1078-0432.CCR-25-3128