Key Messages
What Is Advanced Soft Tissue Sarcoma?
- Soft tissue sarcoma (STS) is a rare type of cancer that starts in the soft tissue of the muscle, fat, lymph vessels, blood vessels, nerves, tendons, and linings of the joints. In adults, less than 1% of all cancers are sarcomas and approximately 80% of sarcoma cases originate from soft tissue. Advanced soft tissue sarcoma (aSTS) refers to STS that has spread or cannot be completely treated by surgery or radiation, and includes unresectable locally advanced and metastatic cancer. Due to its heterogeneity, the clinical course of aSTS varies greatly.
- In Canada, it was estimated that approximately 1,700 people would be diagnosed with STS in 2025, and that approximately 690 people would die from it. There is no published source that directly reported the number of patients with aSTS in Canada in 2025; however, based on approximately 10% to 15% of cases presenting with metastatic disease at diagnosis, it is estimated that there were 100 to 300 cases of metastatic aSTS in Canada in 2025.
What Are the Treatment Goals and Current Treatment Options for aSTS?
- The treatment goals for patients with aSTS is to achieve disease stabilization, delay progression, reduce toxic effects of treatment, and improve health-related quality of life (HRQoL). These have been identified by patient group input as important outcomes. Other important outcomes identified through clinician input include prolonging survival and increasing the ability to maintain independence.
- Current treatment options for adults with aSTS include:
- conventional doxorubicin, either as a single agent or in combination
- epirubicin
- gemcitabine with or without docetaxel
- histological subtype-specific chemotherapies.
What Is Pegylated Liposomal Doxorubicin and Why Did Canada’s Drug Agency Conduct This Review?
- Pegylated liposomal doxorubicin is a specific formulation of the drug doxorubicin hydrochloride. It is administered by IV infusion. Health Canada has approved pegylated liposomal doxorubicin for patients with metastatic breast cancer, advanced ovarian carcinoma, and in AIDS-related Kaposi sarcoma for patients who were intolerant of prior chemotherapy. Pegylated liposomal doxorubicin is used off-label for the treatment of aSTS in Canada.
- At the request of the participating public drug programs, Canada’s Drug Agency (CDA-AMC) reviewed pegylated liposomal doxorubicin to inform a recommendation on whether it should be reimbursed for aSTS.
How Did CDA-AMC Evaluate Pegylated Liposomal Doxorubicin?
- CDA-AMC reviewed the clinical evidence on the beneficial and harmful effects and compared costs of pegylated liposomal doxorubicin versus other treatments used in Canada for aSTS. Conventional doxorubicin (either as a single agent or in combination), epirubicin, gemcitabine with or without docetaxel, and histological subtype–specific chemotherapies were considered relevant treatments to compare with pegylated liposomal doxorubicin.
- The clinical evidence was identified through systematic searches for available studies.
- The review was also informed by 2 patient group submissions in response to our call for input, and by input from the participating public drug programs around issues that may impact their ability to implement a recommendation.
- Two medical oncologists with expertise in the diagnosis and management of STS in adults and adolescents, with representation from Ontario and British Columbia, were consulted as part of the review process.
What Were the Findings?
Clinical Evidence
- CDA-AMC reviewed the following clinical evidence:
- 1 randomized controlled, phase II trial comparing pegylated liposomal doxorubicin with conventional doxorubicin in 95 patients with aSTS
- 1 single-arm, phase II trial evaluating HRQoL outcomes in patients with aSTS treated with pegylated liposomal doxorubicin
- 1 retrospective cohort study comparing pegylated liposomal doxorubicin with conventional doxorubicin in a real-world setting.
- For the comparison of pegylated liposomal doxorubicin versus conventional doxorubicin:
- The evidence was insufficient to demonstrate differences between treatment groups for median progression-free survival and overall survival.
- The evidence was insufficient to demonstrate a difference in objective response rate or stable disease.
- Pegylated liposomal doxorubicin had a lower frequency and less severity of symptoms of myelosuppression, cardiotoxicity, and alopecia. Pegylated liposomal doxorubicin was likely associated with increased risk for palmar-plantar erythrodysesthesia (also known as hand-foot syndrome).
- For evidence on HRQoL without a comparison:
- HRQoL findings for the single-arm, phase II trial were at high risk of bias and had limited interpretability due to the open-label, noncomparative design and loss of observations at follow-up.
- There was no evidence on how pegylated liposomal doxorubicin compares with epirubicin, gemcitabine with or without docetaxel, and histological subtype–specific chemotherapies.
- There was no evidence to inform how pegylated liposomal doxorubicin compares with other available treatments with regard to HRQoL.
Economic Evidence
- Reimbursing pegylated liposomal doxorubicin for aSTS is expected to increase costs to the public drug programs.