Reimbursement Recommendation

Pegylated Liposomal Doxorubicin

Reimbursement request: For the treatment of advanced soft tissue sarcoma in adults

Requester: Public drug programs

Recommendation: Reimburse with conditions

What Is the Reimbursement Recommendation for Pegylated Liposomal Doxorubicin?

The Formulary Management Expert Committee (FMEC) recommends that pegylated liposomal doxorubicin be reimbursed for the treatment of advanced soft tissue sarcoma (aSTS) in adults, provided certain conditions are met.

What Are the Conditions for Reimbursement?

Pegylated liposomal doxorubicin may be initiated and reimbursed for the treatment of aSTS in adults if 1 of the following conditions is met: cardiac contraindications to conventional doxorubicin, poor performance status, or no progression on conventional doxorubicin and having reached the maximum cumulative dose. Pegylated liposomal doxorubicin should be discontinued if there is evidence of disease progression or significant toxicities. The initial prescribing of pegylated liposomal doxorubicin should be limited to medical oncologists with expertise in the management and diagnosis of soft tissue sarcoma (STS). Pegylated liposomal doxorubicin should be priced no higher than the least costly comparator for this population.

Why Did Canada’s Drug Agency Make This Recommendation?

FMEC reviewed 1 phase II randomized controlled trial (RCT), 1 single-arm phase II trial, 1 retrospective cohort study, and a cost comparison of pegylated liposomal doxorubicin versus other treatments used in Canada. The evidence was insufficient to demonstrate clinically important differences between treatment with pegylated liposomal doxorubicin and conventional doxorubicin for overall survival (OS), progression-free survival (PFS), objective response rate, and stable disease.

FMEC concluded that there is a significant clinical need arising from aSTS despite available treatments, largely due to the cardiotoxicity associated with conventional doxorubicin and its maximum lifetime cumulative dose. FMEC also concluded that pegylated liposomal doxorubicin demonstrates acceptable clinical value. The reimbursement recommendation also considered distinct social and ethical considerations, economic considerations, and impacts on health systems.

Review Background

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, sarcomas represent less than 1% of total cancers, and approximately 80% of sarcoma cases originate from soft tissue. Advanced STS (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. The review team estimated that, in 2025, approximately 100 to 300 people in Canada were diagnosed with aSTS and approximately 650 people died from aSTS.

What Are the Current Treatment Options?

Current treatment options for adults with aSTS include:

• conventional doxorubicin, either as a single agent or in combination

• epirubicin, either as a single agent or in combination

• gemcitabine, with or without docetaxel

• histological subtype-specific chemotherapies.

What Is the Treatment Under Review?

Pegylated liposomal doxorubicin is a specific formulation of the drug doxorubicin hydrochloride. It is administered by IV infusion. Pegylated liposomal doxorubicin is used off-label for the treatment of aSTS in Canada.

The reimbursement-requested indication is broader than the Health Canada–approved indication. Health Canada–approved indications for pegylated liposomal doxorubicin are limited to monotherapy for patients with metastatic breast cancer, advanced ovarian carcinoma in people who have experienced treatment failure with standard first-line therapy, and patients with AIDS-related Kaposi sarcoma with disease progression despite chemotherapy or intolerance to prior chemotherapy comprising of at least 2 of the following: a vinca alkaloid, bleomycin, and doxorubicin (or another anthracycline). The request expands the eligible population to those with aSTS.

Why Did We Conduct This Review?

The public drug programs, via the Oncology Working Group, have requested a review of pegylated liposomal doxorubicin for the treatment of STS in adults after the recent closure of the patient assistance program. This is the first Canada’s Drug Agency (CDA-AMC) review of pegylated liposomal doxorubicin. At the request of the participating public drug programs, CDA-AMC reviewed pegylated liposomal doxorubicin to inform a recommendation on whether it should be reimbursed for aSTS.

Highlights of Input From Interested Parties

• Two patient groups, the Canadian Cancer Society and the Sarcoma Cancer Foundation of Canada, highlighted the following important treatment goals: prolonging life, maintaining stable disease, and maintaining quality of life. Patient group input described challenges with accessing care and support services. Responses gathered by the Canadian Cancer Society highlighted the debilitating effects of treatment for aSTS and its impact on patients’ physical and mental health as well as their ability to work and participate in activities of daily living, in addition to the financial and/or emotional strain on both patients and caregivers.

• Public drug plans inquired about the evidence for pegylated liposomal doxorubicin to inform a recommendation for whether it should be reimbursed for the treatment of aSTS in adults. The public drug plans outlined implementation questions related to considerations for treatment initiation, prescribing, generalizability, and care provisions.

Person With Lived Experience

A person from Nova Scotia shared his journey living with STS. The first sign of disease was a growing lump on his leg, which was originally thought to be phlebitis. It was surgically removed in December 2020, and high-grade leiomyosarcoma was diagnosed. A CT scan revealed lung nodules that proliferated then regressed over time, and later reappeared. One nodule ultimately required surgical removal because it was compressing his pulmonary artery. He had a seizure that was caused by a brain tumour, which required surgery, adjuvant radiation, and dexamethasone to treat. He also received radiation for a tumour on his hip. By winter 2024, his lung nodules had progressed to the point that chemotherapy was advised, so doxorubicin was initiated. He did a full course of doxorubicin with the addition of a cardioprotective medication, and after 1 year switched to gemcitabine and docetaxel (his current regimen), which has been effective. He underwent additional radiation for bone metastases. He has experienced a range of treatment side effects, including hair loss, weakness, skin rashes, brain fog, fatigue, and edema. His priority throughout has been to maintain a normal life for his 3 school-aged children. His spouse is extremely supportive, and his employer has been very accommodating of his treatment schedule and needs. He has private insurance through work but is mindful that his out-of-pocket expenses may become substantial if his condition progresses and he requires novel treatments at some point. Knowing that there are other therapies he can access if needed to prolong his life is crucial; having treatment options helps preserve his mental well-being and gives him hope for the future.

Disclaimer: The perspectives shared by people with lived experience who present to the committee reflect their individual experiences and are not necessarily representative of all people with the same condition or course of treatment. Their insights provide valuable context about what a patient, support person, or caregiver might go through when facing this condition or treatment, helping to inform the committee’s deliberations. These narratives complement other forms of evidence and input, and should be considered as part of a broader understanding of the condition and treatment under review. When gender or gendered pronouns are used in these narratives, they are included with the permission of the individual.

Recommendation

With a vote of 8 to 0, the Formulary Management Expert Committee (FMEC) recommends that pegylated liposomal doxorubicin for the treatment of aSTS in adults be reimbursed, if the conditions presented in Table 1 are met.

Table 1: Conditions, Reasons, and Guidance

aSTS = advanced soft tissue sarcoma; FMEC = Formulary Management Expert Committee; STS = soft tissue sarcoma; vs. = versus.

Summary of Deliberation

FMEC deliberated on all domains of value of the deliberative framework before developing its recommendation: clinical value, unmet clinical need, distinct social and ethical considerations, economic considerations, and impacts on health systems. For further information on the domains of value, please refer to the Expert Committee Deliberation at Canada’s Drug Agency document.

FMEC considered the following key discussion points, organized by the 5 domains of value.

Clinical Value

• FMEC concluded that pegylated liposomal doxorubicin demonstrates acceptable clinical value versus appropriate comparators in the Canadian setting.

• Through reflection on the input from patient groups and insights shared by people with lived experience, FMEC members noted that patients value treatments that can extend life while maintaining disease stability and preserving quality of life.

• FMEC members highlighted the following discussion points:

  • The committee acknowledged that STSs are rare cancers, accounting for approximately 1% of all adult cancers. Despite their rarity, STSs and aSTSs have substantial morbidity and mortality and comprise a heterogeneous group of tumour subtypes.

  • Appropriate comparators: Doxorubicin, administered as monotherapy or in combination with other agents, is the standard-of-care first-line treatment for most patients with STS in Canada. FMEC heard from the guest specialists that conventional doxorubicin would be the agent of choice for most patients with aSTS, and that pegylated liposomal doxorubicin would be appropriate in select scenarios.

  • Outcomes assessed: FMEC agreed that clinicians and patients value treatments that stabilize disease, extend survival, reduce treatment-associated toxicity, increase their ability to remain independent, and improve health-related quality of life (HRQoL).

  • Efficacy versus appropriate comparators: FMEC acknowledged evidence from the phase II RCT by Judson et al. (2001) and retrospective cohort study (real-world evidence [RWE]) by Alexio et al. (2026), which demonstrated no difference in efficacy (i.e., overall survival [OS] and progression-free survival [PFS]) between pegylated liposomal doxorubicin and doxorubicin. The committee noted limitations of the clinical evidence, such as the inclusion of aSTS subtypes (e.g., gastrointestinal stromal tumours [GISTs]) that were not expected to respond to doxorubicin, which might reduce the ability of the RCT to detect meaningful differences in efficacy, while excluding GISTs would result in numbers that are too small to draw meaningful conclusions around efficacy. The guest experts confirmed that identification of and treatment for GISTs were not clearly elucidated at the time of the trial, which was published in 2001. At that time, GISTs were still emerging as a distinct entity, and some patients were likely classified as having leiomyosarcoma or other STSs when they would now be diagnosed as having GISTs. Since then, clinical practice has advanced, making misclassification of GISTs as another STS much less common. According to the guest specialists, less than 5% of patients in current clinical practice end up being misclassified as having a GIST. FMEC concluded that the reimbursement focus should shift from efficacy to safety.

  • Harms compared to appropriate comparators: Conventional doxorubicin is associated with cumulative, dose-dependent cardiotoxicity. Pegylated liposomal doxorubicin demonstrated a more favourable safety profile, with both the RCT and RWE study reporting lower rates of myelosuppression and alopecia. The RCT also reported lower rates of cardiotoxicity with pegylated liposomal doxorubicin, although palmar-plantar erythrodysesthesia (hand-foot syndrome) () occurred more frequently with pegylated liposomal doxorubicin than with conventional doxorubicin. FMEC noted that the pegylated liposomal doxorubicin was used in a first-line setting in the RCT, and the guest experts provided additional Canadian context that while pegylated liposomal doxorubicin would be appropriate as first-line treatment in specific subpopulations (due to a more favourable toxicity profile), conventional doxorubicin would be the agent of choice for the majority of cases of aSTS. The rationale provided by the guest experts for the preference of conventional doxorubicin as first-line treatment was that there is a larger volume of randomized data supporting the use of first-line conventional doxorubicin, as well as a historical context for using conventional doxorubicin in this population. The guest experts clarified that cardiotoxicity due to conventional doxorubicin use is relatively uncommon for cumulative doses between 300 mg/m² and 400 mg/m² (with typical rates ranging between 2.5% and 5%). The guest experts clarified that patients are rarely able to tolerate a cumulative dose of conventional doxorubicin beyond 400 mg/m², when cardiotoxicity becomes more likely.

  • FMEC noted that cardioprotective agents were used for patients receiving conventional doxorubicin in the contemporary, US-based RWE study. FMEC heard from the guest specialists that the risk of cardiotoxicity from conventional doxorubicin is relevant when patients reach the upper ranges of cumulative exposure. The guest specialists provided additional Canadian context that cardioprotective agents are uncommonly prescribed due to high cost, and are only used for cases in which patients have approached the maximal cumulative dose for conventional doxorubicin. The guest specialists also provided clarification that the use of cardioprotective agents is based on historical context and mechanism of action.

Unmet Clinical Need

• FMEC concluded that there is a significant clinical need arising from aSTS despite available treatments.

• Through reflection on the input from patient groups and insights shared by people with lived experience, FMEC members noted the multifaceted challenges faced by patients. Patients are faced with the impact of doxorubicin and other chemotherapies on physical appearance, daily function, and quality of life. Patients are anxious about disease progression and uncertain about future treatment options. For individuals with aSTS, having multiple treatment options available is important because disease progression or lifetime exposure limits may necessitate a change in therapy over time. Access to additional therapies can help preserve hope and psychological well-being by reducing uncertainty about future treatment needs. Patient group input highlighted many difficulties associated with the transition to other chemotherapy regimens after patients reach the lifetime dose limit of conventional doxorubicin.

• FMEC members highlighted the following discussion points:

  • Availability of treatment options: Doxorubicin (alone or in combination) is considered the most effective therapy for aSTS. Second-line treatment options include epirubicin, gemcitabine-docetaxel, and other combination chemotherapy regimens.

  • Severity of the disease: FMEC agreed that STS is a rare cancer with high morbidity and toxicities. The Canadian Cancer Society estimated the 5-year relative survival for metastatic aSTS to be approximately 16%.

  • Significant unmet clinical need: An unmet clinical need exists for patients who are unable to tolerate, or have limited tolerance for, the toxicity associated with conventional doxorubicin. This includes younger patients for whom doxorubicin may negatively affect daily function, and patients who require maintenance chemotherapy after reaching the lifetime dose limit for conventional doxorubicin. The committee heard from the guest specialists that patients with demonstrated response to conventional doxorubicin may experience disease progression and resistance to subsequent treatment lines after reaching the maximal lifetime limit and stopping therapy. Pegylated liposomal doxorubicin addresses this unmet need by providing an alternative treatment option with a more favourable toxicity profile and the possibility of maintenance therapy.

  • The guest specialists emphasized that in their clinical practice, the availability of subsequent lines of therapy and the ability to offer options to patients that cannot tolerate conventional doxorubicin were important considerations.

  • Evidence generation: The committee acknowledged that generating high-quality evidence in aSTS is challenging because it comprises a heterogeneous group of tumour subtypes with variable clinical courses and natural history. Treatment selection depends on sarcoma subtype, patient-specific factors, and access to care, making it difficult to conduct large, homogeneous clinical studies.

  • FMEC heard from the guest specialists that younger patients are often more likely to have better functional status and, in clinical practice, would be offered conventional doxorubicin before pegylated liposomal doxorubicin. According to the guest specialists, the most randomized data support the use of conventional doxorubicin as first-line therapy, and pegylated liposomal doxorubicin allows patients to continue with doxorubicin therapy beyond the maximal lifetime dose of conventional doxorubicin. The guest specialists emphasized that an important consideration for younger patients is the ability to maintain their physical appearance throughout therapy, which can support their quality of life.

Distinct Social and Ethical Considerations

• FMEC concluded that pegylated liposomal doxorubicin would not address a significant nonclinical need arising from aSTS despite available treatments.

• FMEC did not identify any important measures that should be implemented to ensure that the use of pegylated liposomal doxorubicin addresses relevant social and ethical implications.

• Through reflection on the input from patient groups and insights shared by people with lived experience, FMEC members noted the importance of patients and caregivers having the knowledge, confidence, and advocacy skills needed to navigate complex diagnoses and treatment pathways. Not all patients have the resources, health literacy, or confidence to effectively advocate for themselves, highlighting the need for equitable support throughout the patient journey.

• FMEC members highlighted the following discussion points:

  • Unmet nonclinical needs. Management of aSTS is typically initiated in specialized treatment centres. Repeated IV infusions may require frequent travel, creating a significant treatment burden for patients, their families, and caregivers.

  • Social and ethical considerations. The committee agreed that the need to travel to specialized treatment centres may disproportionately affect patients from systemically marginalized or equity-deserving populations, potentially creating barriers to equitable access to care.

  • FMEC discussed access to STS specialists and treatment centres across the country. The guest specialists clarified that from a clinical care perspective, family physicians trained in oncology are able to prescribe pegylated liposomal doxorubicin after the initial recommendation from medical oncologists, and care can be provided at smaller treatment sites.

Economic Considerations

• FMEC concluded that there are economic considerations that are important to address when implementing pegylated liposomal doxorubicin, given that pegylated liposomal doxorubicin is a generic drug and its pricing is subject to a defined pan-Canadian Pharmaceutical Alliance tiered pricing framework.

• FMEC members highlighted the following discussion points:

  • Pegylated liposomal doxorubicin is associated with higher costs, similar efficacy, and lower rates and severity of adverse events when compared to doxorubicin.

  • For each 28-day cycle, pegylated liposomal doxorubicin is associated with lower drug costs compared to docetaxel-gemcitabine, doxorubicin-ifosfamide-mesna, epirubicin-ifosfamide-mesna, and paclitaxel.

  • When long-term costs are considered, pegylated liposomal doxorubicin has higher costs compared to all comparators, given that it has no upper limit on the number of cycles. The guest specialists informed the committee that patients typically do not receive more than 6 or 7 cycles of pegylated liposomal doxorubicin, and that the long-term cost issue is likely only relevant in a small number of cases. In patients who receive 6 or fewer cycles, pegylated liposomal doxorubicin is associated with lower drug costs compared to docetaxel-gemcitabine, doxorubicin-ifosfamide-mesna, epirubicin-ifosfamide-mesna, and paclitaxel.

  • Pegylated liposomal doxorubicin is associated with lower rates and severity of adverse events than conventional doxorubicin. This reduction in adverse events may result in health benefits for patients, and decreased costs associated with adverse event management such as unplanned hospitalization and outpatient visits. The committee noted that dexrazoxane may be used as a cardioprotective agent in combination with conventional doxorubicin. The guest specialists informed the committee that few patients receive dexrazoxane in clinical practice, and it is primarily used for patients above the cumulative dose limit of conventional doxorubicin. For patients treated with conventional doxorubicin and dexrazoxane, the cost will be greater than conventional doxorubicin alone. A cost-effectiveness analysis would be needed to properly reflect the magnitude of these health benefits and avoided costs.

  • Given that pegylated liposomal doxorubicin has increased drug acquisition costs and expected similar or unknown clinical benefit to its comparators, it should be priced no higher than the least costly comparator for this population.

Impacts on Health Systems

• FMEC did not identify any impacts on health systems that are important to address when implementing pegylated liposomal doxorubicin.

• FMEC members highlighted the following discussion points:

  • Impacts on health systems: FMEC noted that pegylated liposomal doxorubicin requires a longer infusion time than conventional doxorubicin, which may have implications for infusion site capacity and scheduling. However, patient numbers are expected to be quite small.

  • Considerations for health system sustainability: Given the rarity of STS, the committee anticipated that the use of pegylated liposomal doxorubicin would have a minimal impact on health system infrastructure or human resource requirements.

  • Equity implementation: The committee felt that pegylated liposomal doxorubicin should be made available at all cancer treatment sites (rather than being limited to larger sites), to decrease travel burden for patients, their families, and caregivers.

Sources of Information Used by the Committee

To make its recommendation, the committee considered the following information (links to the full documents for the review can be found on the project web page:

• the CDA-AMC review of the clinical and pharmacoeconomic evidence related to pegylated liposomal doxorubicin (refer to the Main Report and the Supplemental Material document)

• patients' perspectives gathered by 2 patient groups, the Canadian Cancer Society and the Sarcoma Cancer Foundation of Canada (refer to the Patient and Clinician Group Input document)

• input from a person with lived experience who delivered a brief presentation and answered questions from the committee (refer to the Person With Lived Experience section earlier in this document)

• input from public drug programs that participate in the reimbursement review process (refer to the FMEC Responses to Questions From the Drug Program document)

• input from 2 clinical experts consulted by CDA-AMC with expertise in the management of STS in adults and adolescents.

Feedback on Draft Recommendation

CDA-AMC received feedback from 1 clinician group (the Ontario Health [Cancer Care Ontario] Gastrointestinal Cancer Drug Advisory Committee) and the public drug programs. The public drug programs agreed with the recommendation, with no requested revisions. Based on feedback received, editorial revisions were made to the combined clinical and pharmacoeconomic Main Report to clarify why Kaposi sarcoma was not generalizable to this review.

All feedback received in response to the draft recommendation is available on the CDA-AMC project web page.

FMEC Information

Members of the Committee

Dr. Emily Reynen (Chair), Dr. Hardit Khuman (Vice Chair), Dr. Zaina Albalawi, Ms. Marilyn Barrett, Ms. Valerie McDonald, Dr. Bill Semchuk, Dr. Jim Silvius, Dr. Marianne Taylor, Dr. Maureen Trudeau, and Dr. Dominika Wranik

Meeting date: July 16, 2026

Conflicts of interest: None

Special thanks: CDA-AMC extends special thanks to the individuals who presented directly to FMEC and the patient organizations representing and supporting the community of people living with STS, in particular the Canadian Cancer Society, Sasha Frost, and Greg Lee.

Note: CDA-AMC makes every attempt to engage with people with lived experiences as closely to the indication and treatments under review as possible; however, at times, CDA-AMC is unable to do so and instead engages with individuals with similar treatment journeys or experience with comparators under review to ensure lived experience perspectives are included and considered in Reimbursement Reviews. CDA-AMC is fortunate to be able to engage with individuals who are willing to share their treatment journeys with FMEC.