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

Clinical Summary:

• Design/Population: This investigator-initiated, double-blind, placebo-controlled trial evaluated pegylated liposomal doxorubicin in patients with advanced or refractory desmoid tumors. The primary end point was progression-free survival (PFS), with objective response and safety evaluated as secondary end points. 
• Key Outcomes: Pegylated liposomal doxorubicin significantly prolonged PFS compared with placebo, reducing the risk of disease progression or death by approximately 95%. Objective response rates were also significantly higher, with most responders maintaining their responses at data cutoff. 
• Clinical Relevance: These findings provide randomized, phase 3 evidence supporting pegylated liposomal doxorubicin as an additional systemic treatment option for patients with progressive or symptomatic desmoid tumors, particularly when disease control and treatment tolerability are important considerations. 

Results from a phase 3 trial demonstrated that pegylated liposomal doxorubicin significantly improved progression-free survival (PFS) and objective response compared with placebo in patients with advanced or refractory desmoid tumors, supporting its use as an additional systemic treatment option. 

“The clinical course of desmoid tumors is highly variable and often unpredictable, which has led to considerable controversy about its optimal management strategy, especially for patients with progressive or highly symptomatic disease,” stated Huaiyuan Xu, MD, Sun Yat-Sen University Cancer Center, Guangzhou, China, and coauthors. “Pegylated liposomal doxorubicin is a modified anthracycline that reduces cardiotoxicity while preserving antitumor efficacy.” 

In this double-blind trial, placebo-controlled trial, 73 patients with advanced or refractory desmoid tumors who had progressive, symptomatic, or unresectable disease were randomized 2:1 to receive either 50 mg/m² of pegylated liposomal doxorubicin every 4 weeks for up to 6 cycles (n = 47) or placebo (n = 23). Patients assigned to placebo were permitted to cross over to receive pegylated liposomal doxorubicin following disease progression. Treatment continued until completion of the planned cycles, disease progression, or unacceptable toxicity.

The primary end point was investigator-assessed PFS, assessed via RECIST version 1.1. Key secondary end points included confirmed objective response and safety. Tumor response was evaluated using magnetic resonance imaging at baseline and every 3 months.

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. Pegylated liposomal doxorubicin reduced the risk of disease progression or death by 95.2% (hazard ratio [HR], 0.05; 95% confidence interval [CI], 0.01 to 0.17; P < .001).

The estimated 1-year PFS rate was 95.7% in the pegylated liposomal doxorubicin arm and 19.6% in the  placebo arm. The estimated 2-year PFS rates were 90.4% and 19.6%, respectively. The PFS benefit generally favored pegylated liposomal doxorubicin across prespecified subgroups. 

Pegylated liposomal doxorubicin also significantly improved objective response, with confirmed responses observed in 40.4% of patients compared with 4.3% of patients receiving placebo (P = .002). Among patients receiving pegylated liposomal doxorubicin, 8.5% achieved complete response and 31.9% achieved a partial response. One patient in the placebo arm achieved a partial response. 

Tumor shrinkage from baseline was observed in 89.4% of patients in the pegylated liposomal doxorubicin arm. The median best reduction in target lesion diameter was 25.9% with pegylated liposomal doxorubicin, compared with a median increase of 8.1% with placebo. 

Responses with pegylated liposomal doxorubicin were also sustained. At data cutoff, 94.7% of continued to demonstrate a response. Median duration of response was not reached, and median time to response was 11.8 months. 

The safety analysis included 70 patients who received at least 1 dose of study treatment. Adverse events of any grade occurred in 91.5% of patients in the pegylated liposomal doxorubicin arm and 36.4% of patients in the placebo arm. 

Grade 3/4 adverse events were reported in 14.9% of patients receiving pegylated liposomal doxorubicin. The most common events included decreased neutrophil count (10.6%), oral mucositis (6.4%), decreased white blood cell count (4.3%), and palmar-plantar erythrodysesthesia syndrome (2.1%). 

No cardiotoxicities were reported. Among patients treated with pegylated liposomal doxorubicin, adverse events led to 2 dose reductions. Adverse events did not lead to any treatment discontinuations in either treatment arm. 

One patient died in the pegylated liposomal doxorubicin arm from COVID-19–associated pneumonia, which investigators determined was unrelated to study treatment. 

Patient-reported toxicity assessments identified significant between-group differences in decreased appetite, nausea, vomiting, rash, mouth or throat sores, and hand-foot syndrome. These findings provide additional information regarding the treatment burden associated with pegylated liposomal doxorubicin. 

“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 et al. 

Source:

Xu H, Hu J, Zhang Y, et al. Phase 3 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