Reimbursement Recommendation

Bevacizumab

Reimbursement request: In combination with chemotherapy in the second or later line of therapy for patients with recurrent or metastatic endometrial cancer.

Requester: Public drug programs

Final recommendation: Do not reimburse

What Is the Reimbursement Recommendation for Bevacizumab?

The Formulary Management Expert Committee (FMEC) recommends that bevacizumab in combination with chemotherapy not be reimbursed in the second or later line of therapy for patients with recurrent or metastatic endometrial cancer.

Why Did Canada’s Drug Agency Make This Recommendation?

FMEC reviewed 1 trial of bevacizumab plus chemotherapy compared to chemotherapy alone, and a cost comparison of bevacizumab versus other treatments used in Canada. The clinical evidence reviewed demonstrates that bevacizumab has no added benefit compared to standard chemotherapy on overall survival (OS) and progression-free survival (PFS). A higher proportion of patients experienced severe adverse events or discontinued treatment due to adverse events with bevacizumab plus chemotherapy.

Patients and clinicians identified a need for therapies that improve survival, maintain health-related quality of life (HRQoL), and are less toxic than current options in second or later lines of therapy for endometrial cancer. FMEC concluded that bevacizumab in combination with chemotherapy does not demonstrate acceptable clinical value or fill unmet clinical or nonclinical needs identified by patients and clinicians.

Review Background

What Is Endometrial Cancer?

Endometrial cancer is the most common gynecological cancer and originates in the lining of the uterus. The age-standardized incidence rate in 2020 was 34.8 per 100,000. In 2025, 8,600 people were newly diagnosed and 1,700 deaths occurred due to endometrial cancer in Canada. Endometrial cancer significantly impairs physical functioning and HRQoL. The most common symptom of endometrial cancer is abnormal or unusual vaginal bleeding, which may be periodic or continuous. Additional signs and symptoms include pain or feeling of pressure in the pelvis, lower abdomen, back or legs; urinary and bowel dysfunction; and unintentional weight loss.

What Are the Current Treatment Options?

The goal of therapy for patients with recurrent or metastatic endometrial cancer is to improve OS, improve PFS, and improve symptoms as a cure is rarely achievable. Therapeutic approaches for recurrent or metastatic endometrial cancer are mainly driven by molecular profile and disease stage. Systemic treatment options in various lines of therapy include chemotherapy alone, chemotherapy combined with immunotherapy including dostarlimab or pembrolizumab, chemotherapy combined with trastuzumab for HER2-positive tumours, or hormonal therapy.

What Is the Treatment Under Review?

Bevacizumab is a humanized antiangiogenic monoclonal antibody that stops the growth of tumour cells by inhibiting VEGF. At the time this review was conducted, Health Canada has not approved bevacizumab for the treatment of endometrial cancer, and the reimbursement review of bevacizumab is regarded as off-label.

Why Did We Conduct This Review?

At the request of participating public drug programs, Canada’s Drug Agency (CDA-AMC) reviewed bevacizumab to inform a recommendation on whether it should be reimbursed in combination with chemotherapy for second or later lines of therapy for patients with recurrent or metastatic endometrial cancer. Given that there are limited effective therapies for patients with endometrial cancer who progress on first-line or second-line treatments, bevacizumab may help achieve unmet needs in this patient population. Several bevacizumab biosimilars are currently available in Canada, making it eligible for a nonsponsored reimbursement review as per the Procedures for Reimbursement Reviews.

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Highlights of Input From Interested Parties

• Input from Ontario Health (Cancer Care Ontario) Gynecology Cancer Drug Advisory Committee indicated that effective therapies available for patients who progress on first-line or second-line treatment are limited.

• Public drug plans inquired about the evidence for bevacizumab to inform a recommendation on whether bevacizumab in combination with chemotherapy in second or later lines of therapy should be reimbursed for patients with recurrent or metastatic endometrial cancer. The public drug plans outlined implementation questions related to relevant comparators, discontinuation, prescribing, and generalizability.

Person With Lived Experience

A woman in her 60s from Quebec shared her story of living with stage IIIa grade 2 endometrial cancer. She was diagnosed in the fall of 2023 and a few months later underwent a hysterectomy, bilateral salpingo-oophorectomy, and sentinel lymph node dissection before 6 cycles of carboplatin and paclitaxel. She then had 25 rounds of radiation and 1 brachytherapy boost. Side effects of treatment included fatigue, neutropenia, peripheral neuropathy, hair loss, and gastrointestinal issues with some persistent lymphopenia. Managing multiple medical appointments and coordinating care while juggling full-time employment was a logistical challenge and living alone far from family while undergoing treatment was difficult. Today, she has no evidence of disease. She described the ongoing emotional burden of cancer — having to navigate the anxiety that accompanies tests and scans, the shift in personal identity before and after diagnosis, and the transition to survivorship, which requires a different kind of vigilance. She feels fortunate to have been able to access excellent medical care, to have flexibility with her job, a high level of health literacy and comfort advocating for herself, and private insurance, which covered most of her treatment costs. Online support groups and forums have been instrumental in helping her understand her own and others’ experience of cancer and resume activities she is deeply passionate about, like running.

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 9 to 0, FMEC does not recommend that bevacizumab in combination with chemotherapy in the second or later line of therapy for patients with recurrent or metastatic endometrial cancer be reimbursed by publicly funded drug plans.

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 bevacizumab with chemotherapy does not demonstrate acceptable clinical value versus appropriate comparators in the setting in Canada.

• Through reflection on the insights shared by the person with lived experience, FMEC members noted that patients want more time and meaningful disease control. Patients value quality of life (e.g., ability to maintain normalcy), manageable side effects, and having treatment options when disease progresses.

• FMEC members highlighted the following discussion points:

  • Appropriate comparators. The MITO END-2 trial compared chemotherapy plus bevacizumab versus chemotherapy. There are current treatment options for second-line therapy which were not comparators in the trial, such as pembrolizumab for deficient mismatch repair cancers and pembrolizumab plus lenvatinib for proficient mismatch repair tumours.

  • Outcomes assessed. The committee agreed that the outcomes assessed in the MITO END-2 trial (PFS, overall response rate, OS, and HRQoL) are all important outcomes for patients.

  • Efficacy compared to appropriate comparators. FMEC agreed that the trial did not show any positive results in any of the clinical efficacy outcomes assessed. The evidence was insufficient to show a difference in PFS or OS for bevacizumab plus carboplatin and paclitaxel compared with carboplatin and paclitaxel alone. Between-group differences for overall response rate and disease control rate were not reported nor tested statistically. Although assessment of HRQoL was planned by study authors, they were unable to analyze this outcome due to low response rates.

  • Harms. The committee agreed that toxicity was increased with chemotherapy plus bevacizumab compared to chemotherapy alone.

  • Level of certainty in clinical value. The committee decided that there were no clear clinical benefits to adding bevacizumab to chemotherapy and that this therapy was associated with increased toxicity. The findings of the MITO END-2 trial are uncertain due to risk of bias and imprecision. Approximately 80% of patients included in the trial were in a different line of therapy (first-line therapy) than the funding request (second and subsequent lines of therapy), which also increases uncertainty in the evidence due to indirectness.

  • FMEC heard the guest specialists explain that bevacizumab is not a treatment that they typically use in clinical practice. Bevacizumab may be best suited for a niche group of patients (e.g., patients with TP53 mutations); however, there was no data available in this subgroup for FMEC to review (i.e., there was no subgroup analysis in patients with TP53 mutations in the MITO END-2 trial).

Unmet Clinical Need

• FMEC concluded that there is a significant clinical need arising from recurrent or metastatic endometrial cancer despite available treatments; however, bevacizumab with chemotherapy does not address this need.

• Through reflection on the insights shared by the person with lived experience, FMEC members noted the large treatment burden due to logistics, coordination of care, and emotional impacts. The person with lived experience also shared having to deal with anxiety and persistent lymphopenia and neutropenia, and that transition to survivorship is also a process for patients.

• FMEC members highlighted the following discussion points:

  • Availability of treatment options. The committee agreed there were alternative therapies but were unsure of how effective these therapies are in the second and subsequent lines of therapy as this evidence was not reviewed. Input from the clinician group and guest specialists suggested that there was poor control of endometrial cancer with these types of therapies.

  • Severity of the disease. The committee agreed that recurrent or metastatic uterine cancer is incurable and is associated with significant morbidity.

  • Significant unmet clinical need. The committee agreed there was a need for alternative therapies that are superior or less toxic to the current options in second line. Recurrent or metastatic uterine cancer is incurable and is associated with significant morbidity. FMEC agreed that the addition of bevacizumab to chemotherapy did not address these unmet needs, due to the findings of the MITO END-2 trial (no impact on clinical efficacy and increased harms) and the low certainty of the evidence.

  • Evidence generation. The committee did not believe there were issues in generating evidence for the treatment of advanced uterine cancers.

  • The guest specialists shared that a phase III trial (NRG-GY035) in patients with advanced or recurrent proficient mismatch repair, TP53-mutated endometrial cancer was recently launched (study started January 2026; expected study completion July 2028). The trial has 3 treatment arms:

    • Comparator arm: Carboplatin plus paclitaxel plus pembrolizumab, followed by maintenance therapy with pembrolizumab alone.

    • Intervention arm: Carboplatin plus paclitaxel plus pembrolizumab, followed by maintenance therapy with bevacizumab alone.

    • Intervention (quadruplet) arm: Carboplatin plus paclitaxel plus pembrolizumab, followed by maintenance therapy with both pembrolizumab and bevacizumab.

Distinct Social and Ethical Considerations

• FMEC concluded that bevacizumab with chemotherapy would not address a significant nonclinical need arising from recurrent or metastatic endometrial cancer despite available treatments.

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

• Through reflection on the insights shared by the person with lived experience, FMEC members noted the importance of being able to navigate health care systems and patient advocacy. Even patients living in a major city with leading hospitals, with flexible work schedules, and private insurance experience substantial gaps in access to care, such as prediagnosis awareness, return to activity guidance, nutritional information, and access to support groups.

• FMEC members highlighted the following discussion points:

  • Significant unmet nonclinical need. The committee did not believe that bevacizumab addressed unmet nonclinical needs for endometrial cancer.

  • Social or ethical implications. FMEC agreed that bevacizumab does not address relevant ethical or social implications.

Economic Considerations

• FMEC reviewed the economic considerations for bevacizumab. Given that bevacizumab was not recommended for reimbursement based on unacceptable clinical value and failure to address a significant unmet need, further deliberation on economic considerations was not required.

Impacts on Health Systems

• FMEC reviewed the impacts on health systems when implementing bevacizumab. Given that bevacizumab was not recommended for reimbursement based on unacceptable clinical value and failure to address a significant unmet need, further deliberation on measures to address these impacts was not required.

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 webpage):

• the CDA-AMC review of the clinical and pharmacoeconomic evidence related to bevacizumab (refer to the main report and the Supplemental Material)

• 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)

• input from 1 clinician group: Ontario Health (Cancer Care Ontario) Gynecology Cancer Drug Advisory Committee

• input from public drug programs that participate in the reimbursement review process

• input from 2 guest specialists with expertise in the management of endometrial cancer consulted by CDA-AMC.

Feedback on Draft Recommendation

CDA-AMC received feedback from 1 clinician group (Ontario Health [Cancer Care Ontario]) and the public drug programs. Both groups agreed with the recommendation, with no requested revisions.

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

FMEC Information

Members of the Committee

Dr. Emily Reynen (Chair), Dr. Zaina Albalawi, Ms. Marilyn Barrett, Dr. Hardit Khuman, Ms. Valerie McDonald, Dr. Bill Semchuk, Dr. Jim Silvius, Dr. Marianne Taylor, Dr. Maureen Trudeau, Dr. Dominika Wranik. Two guest specialists from the Atlantic region and the Prairies participated in this review.

Meeting date: January 22, 2026

Conflicts of interest: None.

Special thanks: Canada’s Drug Agency (CDA-AMC) extends special thanks to the individuals who presented directly to FMEC and to patient organizations representing and supporting the community of people living with endometrial cancer, including the Canadian Cancer Society, Sasha Frost, and Brenda Sanderson.

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.