Reimbursement Recommendation

Tislelizumab (Tevimbra)

Indication: In combination with gemcitabine and cisplatin for the first-line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma

Sponsor: BeOne Medicines (Canada) ULC

Recommendation: Reimburse with conditions

What Is the Reimbursement Recommendation for Tevimbra?

Canada’s Drug Agency (CDA-AMC) recommends that Tevimbra be reimbursed by public drug plans, in combination with gemcitabine and platinum chemotherapy, for the first-line treatment of adult patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) if certain conditions are met.

Why Did CDA-AMC Recommend Reimbursement?

Evidence from 1 clinical trial showed that Tevimbra, in combination with gemcitabine-cisplatin in the first-line setting, improved progression-free survival (PFS) and overall survival (OS) compared with gemcitabine-cisplatin alone in patients with recurrent or metastatic NPC. The pan-Canadian Oncology Drug Review Expert Review Committee (pERC) determined that adding Tevimbra to gemcitabine plus platinum chemotherapy provides acceptable clinical value compared with gemcitabine plus platinum chemotherapy alone for the first-line treatment of recurrent or metastatic NPC. pERC also determined that Tevimbra in combination with gemcitabine and platinum chemotherapy addresses the need identified by both patients and clinicians for a more effective first-line therapy to delay disease progression and extend survival. These determinations were enough for pERC to recommend that Tevimbra be reimbursed. Given that Tevimbra is expected to be used as an add-on to gemcitabine plus platinum chemotherapy, acceptable clinical value reflects its added benefit over gemcitabine plus platinum chemotherapy alone.

Which Patients Are Eligible for Coverage?

Tevimbra in combination with gemcitabine plus platinum chemotherapy should only be covered for adults with recurrent or metastatic NPC that cannot be treated with surgery or curative radiation and who have not received any previous systemic treatment for the condition. Patients should have good performance status and should not have active or uncontrolled cancer in the brain or significant autoimmune disease.

What Are the Conditions for Reimbursement?

Tevimbra in combination with gemcitabine plus platinum chemotherapy should only be reimbursed if the patient is under the care of a clinician who has expertise in managing NPC and side effects of immunotherapy and the cost of Tevimbra is reduced. Treatment should be discontinued if the patient experiences disease progression or unacceptable side effects.

Important organizational implications must be addressed for health systems to be able to adopt Tevimbra.

Review Background

• Disease background:

  • NPC is a cancer that arises from the lining of the nasopharynx. It causes a range of symptoms and can substantially affect health-related quality of life (HRQoL).

  • NPC is rare in North America but occurs more frequently in the Arctic, North Africa, Southeast Asia, and Southern China. In Canada (excluding Quebec), the 5-year prevalence was 840 cases in 2018, equivalent to approximately 3 per 100,000 people.

• Indication and reimbursement request: Tislelizumab (Tevimbra) has been approved by Health Canada for use in combination with gemcitabine and cisplatin for the first-line treatment of adult patients with recurrent or metastatic NPC. The sponsor is seeking reimbursement for this patient population. This application was submitted by the sponsor before receiving a Notice of Compliance from Health Canada. The CDA-AMC review reflects the sponsor’s originally proposed indication and product monograph, which generally aligned with the final approved indication.

• Drug under review: Tislelizumab is a PD-1 inhibitor. It is available as a concentrate for solution for administration by IV infusion. The dosage recommended in the product monograph is 200 mg once every 3 weeks in combination with cisplatin and gemcitabine chemotherapy for 4 to 6 cycles, after which it is continued as monotherapy until unacceptable toxicity or disease progression occurs. The Health Canada–approved product monograph for tislelizumab includes a Serious Warnings and Precautions Box outlining the risks of immune-mediated adverse reactions, infusion-related reactions, and complications in patients who receive allogeneic hematopoietic stem cell transplant.

• Treatment costs: At the submitted price of $3,080.00 per vial, the 21-day cycle cost of tislelizumab is expected to be $6,160 per patient, based on the Health Canada–recommended dosage. When used in combination with chemotherapy, the 21-day cycle cost of tislelizumab plus chemotherapy is expected to be $7,645 for the first 6 cycles and $6,160 for subsequent cycles. When considering a 28-day cost, tislelizumab is expected to cost $8,213 per patient and $10,193 per patient when used in combination with chemotherapy.

Highlights of Input From Interested Parties

Three patient groups (the Canadian Organization for Rare Disorders, the Canadian Cancer Survivor Network, and the Canadian Cancer Society) jointly provided the following input on the impact of the disease, unmet needs, and important outcomes:

• In a survey of patients with NPC and their caregivers, nearly half of respondents reported that NPC had a moderate to severe impact on their overall HRQoL, with effects on physical health, emotional well-being, mental health, social interactions, work or daily activities, quality of sleep, nutritional intake, and pain and discomfort noted. The patient groups noted that disease symptoms such as fatigue, hearing loss, changes in visual appearance, breathing difficulties, and sleep disturbance could significantly impair patients’ social interactions and daily activities.

• The survey respondents emphasized the need for effective first-line and second-line therapies for these patients, who currently have few treatment options. The patient groups identified improving survival, HRQoL, and symptom management and minimizing side effects as the most important treatment outcomes.

The clinician groups that provided input (Ad Hoc Treaters of NPC and the Ontario Health [Cancer Care Ontario] Head and Neck Cancer Drug Advisory Committee) and the clinical experts consulted by CDA-AMC identified the following unmet needs and considerations regarding the disease and the place in therapy for the drug under review:

• Although NPC is initially chemosensitive, the current first-line treatment with gemcitabine and platinum chemotherapy is associated with treatment resistance, disease progression, and both acute and long-term side effects. Therefore, there is a significant unmet need for additional, more effective treatment options.

• Clinical experts anticipate that tislelizumab in combination with gemcitabine and platinum chemotherapy could establish a new standard of care for the first-line treatment of patients with recurrent or metastatic NPC.

The participating public drug programs raised potential implementation issues related to considerations for discontinuation and prescribing of therapy; generalizability of trial populations to broader populations; system and economic issues; and the potential need for a Provisional Funding Algorithm. A table summarizing these issues can be found in the Supplemental Material document on the project landing page.

Person With Lived Experience

A person with lived experience from Manitoba shared her journey with late-stage nasopharyngeal carcinoma, having been diagnosed when aged 17 years. She described months of biopsies before surgery confirmed cancer, which was followed by chemotherapy and 7 weeks of daily radiation to her face and neck. She described radiation therapy as an extremely difficult experience, causing severe throat burns, jaw issues, and a sudden loss of taste. She faced unexpected decisions about fertility preservation, which added stress and financial pressure during an already overwhelming time. Long-distance travel for care created logistical and emotional challenges for her family. She emphasized how isolation, uncertainty, and expenses compounded the burden but emphasized that she was willing to make repeated 4-hour round trips to Winnipeg because getting better was her priority.

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 with 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 1 element contributing to a broader understanding of the condition and treatment under review.

Recommendation

With a vote of 14 in favour to 0 against, pERC recommends that tislelizumab be reimbursed, in combination with gemcitabine and platinum chemotherapy, for the first-line treatment of adult patients with recurrent or metastatic NPC only if the conditions listed in Table 1 are met.

Table 1: Reimbursement Conditions and Reasons

CDA-AMC = Canada’s Drug Agency; CNS = central nervous system; ECOG = Eastern Cooperative Oncology Group; ICER = incremental cost-effectiveness ratio; NPC = nasopharyngeal carcinoma; pERC = pan-Canadian Oncology Drug Review Expert Review Committee; PS = performance status; QALY = quality-adjusted life-year.

^aIn the economic evaluation, chemotherapy was specified as gemcitabine plus either cisplatin or carboplatin.

^bFor the statement regarding the size of the price reduction required, band 1 = 1% to 24%, band 2 = 25% to 49%, band 3 = 50% to 74%, and band 4 = 75% or greater.

Rationale for the Recommendation

Clinical Value

Based on the totality of the clinical evidence, pERC concluded that tislelizumab in combination with gemcitabine and platinum chemotherapy demonstrates acceptable clinical value compared with gemcitabine plus platinum chemotherapy alone in the first-line treatment of patients with recurrent or metastatic NPC. Given that tislelizumab is expected to be an add-on treatment to gemcitabine plus platinum chemotherapy, acceptable clinical value refers to incremental value compared to gemcitabine plus platinum chemotherapy.

Evidence from 1 randomized, double-blind, placebo-controlled, multicentre phase III trial (RATIONALE-309; N = 263) demonstrated that first-line treatment with tislelizumab in combination with gemcitabine-cisplatin likely results in added clinical value in PFS and OS for patients with recurrent or metastatic NPC compared to placebo plus gemcitabine-cisplatin. After a median follow-up time of 33.3 months for the tislelizumab plus gemcitabine-cisplatin group and 25.0 months for the placebo plus gemcitabine-cisplatin group, the median PFS per independent review committee (primary end point) was 9.6 months (95% confidence interval [CI], 7.6 months to 11.6 months) in the tislelizumab plus gemcitabine-cisplatin group and 7.4 months (95% CI, 5.6 months to 7.6 months) in the placebo plus gemcitabine-cisplatin group (stratified hazard ratio [HR] = 0.53; 95% CI, 0.39 to 0.71). At 36 months, the Kaplan-Meier (KM) estimates of the probability of PFS were 17.4% (95% CI, 10.7% to 25.5%) in the tislelizumab plus gemcitabine-cisplatin arm and 6.3% (95% CI, 2.7% to 12.0%) in the placebo plus gemcitabine-cisplatin arm, with a between-group difference of 11.1% (95% CI, 2.3% to 19.9%). The KM estimates of the probability of OS (secondary end point) at 36 months was 55.6% (95% CI, 46.0% to 64.1%) and 46.4% (95% CI, 36.9% to 55.3%), respectively, with a between-group difference of 9.2% (95% CI, −3.8% to 22.2%).

Patient groups, clinician groups, and clinical experts consulted by CDA-AMC identified the need for treatments that are more effective in prolonging survival and delaying disease progression while also controlling symptoms, improving quality of life, and minimizing side effects. pERC concluded that tislelizumab, when added to gemcitabine and platinum chemotherapy, addresses the need for a more effective treatment that may delay disease progression and prolong survival. In the RATIONALE-309 trial, little to no difference in HRQoL was shown between the tislelizumab plus gemcitabine-cisplatin group and the placebo plus gemcitabine-cisplatin group. However, pERC was unable to draw conclusions on HRQoL due to the high amount of missing data. In the trial, a higher proportion of patients in the tislelizumab plus gemcitabine-cisplatin group experienced immune-mediated adverse events (imAEs) than in the placebo plus gemcitabine-cisplatin group. The committee agreed with the clinical experts that the types of AEs in the trial were as expected for immunotherapy combined with gemcitabine-cisplatin.

Additional information on the committee’s discussion around clinical value is provided in the Summary of Deliberation section.

Developing the Recommendation

The determination of acceptable clinical value was sufficient for pERC to recommend reimbursement of tislelizumab. As part of the deliberation on whether to recommend reimbursement, the committee also considered unmet clinical need, unmet nonclinical need, and health inequity. Information on this discussion is provided in the Unmet Clinical Need and Distinct Social and Ethical Considerations domains in the Summary of Deliberation section.

Because pERC recommended that tislelizumab be reimbursed, the committee also deliberated on whether reimbursement conditions should be added to address important economic considerations, health system impacts, or social and ethical considerations to ensure clinical value is realized. The resulting reimbursement conditions, with accompanying reasons and implementation guidance, are stated in Table 1.

Summary of Deliberation

pERC considered all domains of value in 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, refer to Expert Committee Deliberation at Canada’s Drug Agency.

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

Clinical Value

• Appropriate comparators: pERC considered the combination of gemcitabine and platinum (i.e., cisplatin or carboplatin) chemotherapy to be an appropriate comparator, as gemcitabine plus platinum chemotherapy is the current standard first-line treatment for patients with recurrent or metastatic NPC.

• Efficacy versus gemcitabine-cisplatin: The phase III RATIONALE-309 trial demonstrated that first-line treatment with tislelizumab plus gemcitabine-cisplatin resulted in a statistically significant and clinically meaningful improvement in the primary end point of median PFS compared to placebo plus gemcitabine-cisplatin (HR = 0.53; 95% CI, 0.39 to 0.71). At 9 months, the KM estimates of PFS probability were 52.7% (95% CI, 43.4% to 61.2%) in the tislelizumab plus gemcitabine-cisplatin arm versus 26.1% (95% CI, 18.3% to 34.5%) in the placebo plus gemcitabine-cisplatin arm, with a between-group difference of 26.6% (95% CI, 14.5% to 38.8%). At 36 months, the probabilities of PFS were 17.4% (95% CI, 10.7% to 25.5%) and 6.3% (95% CI, 2.7% to 12.0%), respectively, with a between-group difference of 11.1% (95% CI, 2.3% to 19.9%). For OS, after a median follow-up of 41.4 months in the tislelizumab plus gemcitabine-cisplatin group and 40.8 months in the placebo plus gemcitabine-cisplatin group, median OS was 45.3 months (95% CI, 33.4 months to not evaluable) in the tislelizumab plus gemcitabine-cisplatin group and 31.8 months (95% CI, 25.0 months to not evaluable) in the placebo plus gemcitabine-cisplatin group (HR = 0.73; 95% CI, 0.51 to 1.05). The absolute differences in the estimated OS probabilities between the tislelizumab plus gemcitabine-cisplatin and placebo plus gemcitabine-cisplatin groups were 4.7% (95% CI, −3.7% to 13.0%) at 12 months and 9.2% (95% CI, −3.8% to 22.2%) at 36 months. HRQoL, as assessed by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Global Health Status and Quality of Life scores, showed little to no difference between the tislelizumab plus gemcitabine-cisplatin group and the and placebo plus gemcitabine-cisplatin group. However, conclusions regarding HRQoL outcomes could not be drawn due to missing data and the potential for unblinding treatment allocation upon confirmed disease progression.

• Clinical importance of treatment effects: pERC considered outcomes of importance identified by patient groups and clinicians, which include prolonging life, delaying cancer progression, relieving symptoms, improving quality of life, and avoiding treatments with severe side effects. Thresholds for clinically meaningful between-group differences were suggested by the clinical experts consulted by CDA-AMC for the probability of PFS at 9 months and 36 months (10 to 15 percentage points) and for the probability of OS at 12 months and 36 months (5 to 10 percentage points). The difference in the probability of survival in the tislelizumab plus gemcitabine-cisplatin group compared to the placebo plus gemcitabine-cisplatin group approached this threshold at 12 months and exceeded it at 36 months, indicating a clinically meaningful difference in OS between groups at these time points. In addition, pERC acknowledged input from clinical experts that the median OS benefit with tislelizumab was of clinically meaningful value.

• Certainty of the evidence: pERC discussed the certainty of evidence as assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method. For the added PFS value, the certainty was rated as high at 9 months, indicating a clinically important improvement in PFS with the addition of tislelizumab to gemcitabine-cisplatin chemotherapy at this time point. The certainty for the added PFS value at 36 months was rated down to moderate for imprecision, because the 95% CI for the difference between groups includes the possibility of little to no clinically meaningful difference. The certainty for the added value of OS was rated as moderate at both 12 months and 36 months, suggesting that the addition of tislelizumab to gemcitabine-cisplatin chemotherapy likely results in a clinically important improvement in survival. The certainty of evidence at each time point was rated down for imprecision. pERC noted that more than half of patients in the placebo plus gemcitabine-cisplatin group crossed over to receive tislelizumab after disease progression (as second-line treatment), which is not reflective of current clinical practice in Canada. This crossover likely diluted the observed OS benefit, meaning the true effect of tislelizumab may be underestimated. However, this was not rated down due to indirectness because the magnitude of the between-group difference is unlikely to be smaller than reported. Statistical analyses were performed to investigate the impact of crossover on OS, and the committee considered these analyses when interpreting the OS results. pERC additionally noted that some subsequent therapies used in the trial are not available in Canada, adding to uncertainty. The analyses of both PFS and OS violated the proportional hazards assumption, meaning the HR was not constant over time. pERC acknowledged that reliance on the HR alone to interpret the effect of tislelizumab plus gemcitabine-cisplatin versus placebo plus gemcitabine-cisplatin may be misleading. However, between-group differences in KM estimated probabilities of PFS and OS at prespecified time points, which were used to assess certainty of evidence, are not affected by this limitation. The certainty of evidence for EORTC QLQ‑C30 Global Health Status and Quality of Life scores was rated as moderate at cycle 4 and low at cycle 8, suggesting that the addition of tislelizumab to gemcitabine-cisplatin chemotherapy likely results in little to no difference in HRQoL at cycle 4 and may result in little to no difference in HRQoL at cycle 8. The certainty of evidence for serious AEs was rated as low, as the 95% CI for the difference between groups spans from a possible benefit to possible harm.

• Comparative harms: pERC discussed harms results from the RATIONALE-309 trial, which included similar proportions of patients with overall treatment-emergent AEs and serious AEs in the tislelizumab plus gemcitabine-cisplatin and placebo plus gemcitabine-cisplatin groups, but higher rates of imAEs and more deaths due to AEs in the tislelizumab plus gemcitabine-cisplatin arm. The committee acknowledged input from clinical experts indicating that the types of AEs observed in the RATIONALE-309 trial were consistent with expectations for immunotherapy combined with gemcitabine-cisplatin, and that imAEs are considered generally manageable in clinical practice.

• Generalizability: pERC discussed that all patients enrolled in the RATIONALE-309 trial were of Asian descent, and that other populations affected by NPC in Canada (e.g., Inuit patients) were not represented. While generalizability of the trial results to the population in Canada may be uncertain, the committee acknowledged input from clinical experts that the distribution of histology types in the trial reflects what is typically observed in practice in Canada. The experts considered the results of the trial to be generalizable to patients who are not Asian.

• Clinical value: Based on the preceding considerations, pERC determined that there was added clinical value for tislelizumab in combination with gemcitabine and platinum chemotherapy versus gemcitabine plus platinum chemotherapy alone. Although the chemotherapy regimen used in the RATIONALE-309 trial included cisplatin, pERC agreed with the clinical experts that carboplatin would be a reasonable alternative to cisplatin and is already used in combination with gemcitabine for the treatment of recurrent or metastatic NPC in many jurisdictions.

Unmet Clinical Need

• Input on unmet clinical need: Patient groups, clinician groups, and clinical experts consulted by CDA-AMC identified an unmet need for treatments that are more effective in prolonging life and delaying disease progression while also controlling symptoms, improving quality of life, and minimizing treatment-related AEs.

• Severity of the disease: pERC discussed input from patient groups indicating that recurrent or metastatic NPC is associated with serious symptoms and imposes substantial burden on multiple aspects of life including physical health, emotional well-being and mental health, social interactions, work or daily activities, sleep, nutrition, and pain. The committee also acknowledged that the disease prognosis for recurrent or metastatic NPC is poor, and recurrent or metastatic NPC is associated with substantial mortality.

• Availability of treatment options: Currently, the standard first-line treatment for recurrent or metastatic NPC is gemcitabine plus platinum chemotherapy, which is publicly funded in Canada. Other chemotherapy agents may be considered for patients who are not candidates for this regimen. Palliative radiation therapy may also be used. The patient group input also highlighted that radiation therapy often involves burdensome treatment schedules and side effects, including localized pain and discomfort in the treated area. Patients expressed hope that adding tislelizumab to chemotherapy as a first-line treatment for recurrent or metastatic NPC could help eligible patients avoid the need for radiation therapy. pERC additionally considered input from clinical experts consulted by CDA-AMC and clinician groups who emphasized that, although NPC is initially chemosensitive, not all patients experience a disease response to treatment, and disease responses are not durable. Clinical experts also noted that toxicity from gemcitabine plus platinum chemotherapy can include both short- and long-term effects, is often cumulative, and may negatively affect quality of life.

Distinct Social and Ethical Considerations

• Input on unmet nonclinical need: pERC acknowledged there are unmet nonclinical needs of patients with recurrent or metastatic NPC. Input from patient groups highlighted that current treatments are associated with severe side effects (e.g., changes in smell or taste, loss of appetite, fatigue, neuropathy, hearing loss, radiation burns, weight loss) that have a substantial impact on quality of life. The committee also recognized the financial burden of treatment for NPC on patients and caregivers, including costs related to travel, meal replacements, medications to manage AEs, and loss of income due to having to take time off from work. Individuals with lower incomes were noted to experience the greatest financial hardship.

• Equity considerations: pERC noted that NPC disproportionately affects Inuit and some immigrant populations from regions with higher risk for the disease (i.e., the Arctic, East and Southeast Asia, and North Africa) who may already face barriers to diagnosis, access to care, and equitable outcomes due to financial, language, or cultural challenges. Given the higher incidence of NPC among Inuit who may reside in remote areas, considerable travel may be required for these patients to receive care (including diagnosis, imaging, and systemic therapy). pERC also discussed that adding tislelizumab to platinum-based chemotherapy may increase the number of appointments for patients as tislelizumab is administered until progressive disease or unacceptable toxicity occurs, rather than being administered as a fixed number of cycles. Furthermore, due to the small number of eligible patients and the short stability of the drug preparation, the administration of tislelizumab may be limited to select locations within jurisdictions. pERC acknowledged that these factors could introduce additional barriers and burden (e.g., travel and related expenses) for patients and caregivers. The committee emphasized that resources to support patient travel and accommodations would be necessary to ensure equitable access and continuity of treatment.

• pERC considered the unmet nonclinical needs and health inequities affecting patients with recurrent or metastatic NPC and determined that these are not necessarily addressed by tislelizumab.

Economic Considerations

• Health impacts of tislelizumab plus chemotherapy versus relevant comparators: Tislelizumab plus chemotherapy is predicted to be associated with a gain of 1.29 life-years and 0.87 quality-adjusted life-years (QALYs) compared to chemotherapy alone.

• Cost of tislelizumab plus chemotherapy versus relevant comparators: Tislelizumab plus chemotherapy is predicted to be associated with higher costs to the health care system than chemotherapy alone (incremental costs = $107,597), primarily due to higher drug acquisition costs (incremental drug acquisition costs = $97,372). Additional cost increases are also attributed to drug administration and disease management associated with tislelizumab use.

• Key findings of the economic evaluation: Based on the sponsor’s cost-utility analysis, the CDA-AMC base-case analysis estimated that the incremental cost-effectiveness ratio for tislelizumab plus chemotherapy for first-line treatment of patients with recurrent or metastatic NPC was $124,171 per QALY gained when compared with chemotherapy alone (Figure 1).

• The committee discussed that NPC may disproportionately affect Inuit and some immigrant populations from regions with higher risk for the disease and those living in rural and remote settings. Given that this treatment is likely to be administered only in cancer centres with a compounding pharmacy, the committee noted that this may introduce additional costs to patients and the public health system (e.g., travel and accommodation, preparation of the product for administration). The economic analysis did not incorporate these costs incurred by patients or the public health system. The cost-effectiveness of tislelizumab when considering these additional costs is unknown.

  Figure 1: Estimate of the ICER Used by pERC to Inform the Price Condition

  

  ICER = incremental cost-effectiveness ratio; pERC = pan-Canadian Oncology Drug Review Expert Review Committee; QALY = quality-adjusted life-year.

• Certainty of the evidence: pERC identified uncertainty in the cost-effectiveness of tislelizumab plus chemotherapy due to limitations in the long-term comparative efficacy data, survival projections, and structure of the submitted economic model. Additionally, the model predicted a postprogression benefit for tislelizumab plus chemotherapy. While clinical experts noted that immunotherapies may provide some residual postprogression survival, both the duration and magnitude of this benefit remain uncertain in the absence of long-term evidence. As a result, the economic analysis may not fully reflect the true impact of tislelizumab plus chemotherapy on patient outcomes and health care resources. Thus, the cost-effectiveness of tislelizumab plus chemotherapy remains uncertain, and greater price reductions may be required to achieve a given willingness-to-pay threshold.

• Other considerations: Toripalimab in combination with cisplatin and gemcitabine is currently under review by CDA-AMC for the first-line treatment of adults with metastatic NPC or recurrent, locally advanced NPC. The cost-effectiveness of tislelizumab compared to toripalimab in this patient population is unknown. Furthermore, the potential budget impact of funding other treatments for this indication, such as toripalimab, has not been determined.

Impacts on Health Systems

• Anticipated budget impact: CDA-AMC estimated that 419 patients would be eligible for treatment with tislelizumab plus chemotherapy over a 3-year period (year 1 = 135; year 2 = 140; year 3 = 144), of whom 391 are expected to receive tislelizumab plus chemotherapy (year 1 = 122; year 2 = 133; year 3 = 137). The estimated incremental budget impact of reimbursing tislelizumab plus chemotherapy is predicted to be approximately $25,979,875 over the first 3 years, with an expected expenditure of $28,501,534 on tislelizumab plus chemotherapy.

• Organizational implications: Public drug plans raised concerns about the potential budget impact of reimbursing tislelizumab, noting there are several patients currently accessing tislelizumab through Health Canada’s Special Access Program. If tislelizumab is reimbursed, these patients would likely transition to public funding and, as such, may lead to a higher budget impact than estimated by the sponsor.

• Equity considerations: As previously stated, pERC acknowledged that for patients who reside in remote settings, considerable travel may be required to receive care (including diagnosis, imaging, and systemic therapy). Furthermore, factors related to tislelizumab dosing and stability of the final preparation could introduce additional barriers and burdens for patients and caregivers. The committee stated that resources required to support patient travel and accommodations would need to be addressed to ensure equitable access and intended duration of treatment.

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 submitted by the sponsor, as well as relevant ethical issues related to tislelizumab (refer the Main Report and Supplemental Material documents)

• the sponsor’s comments on the draft report and the CDA-AMC responses

• patients' perspectives gathered by 3 patient groups — the Canadian Organization for Rare Disorders, the Canadian Cancer Survivor Network, and the Canadian Cancer Society (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 2 clinician groups, Ad Hoc Treaters of NPC and the Ontario Health (Cancer Care Ontario) Head and Neck Cancer Drug Advisory Committee (refer to the Patient and Clinician Group Input document)

• input from public drug programs that participate in the reimbursement review process (refer to the Supplemental Material document)

• input from 3 clinical experts with expertise in the management of NPC consulted by CDA-AMC.

Special thanks: CDA-AMC extends special thanks to the individual who presented directly to pERC and to the patient organizations representing the community of those living with NPC, including the Canadian Cancer Society, which includes Raven Verano and Sasha Frost.

General note: CDA-AMC makes every attempt to engage with people with lived experience as closely to the indication under review as possible; however, at times, CDA-AMC is unable to do so and instead engages with individuals with similar treatment journeys 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 pERC.

pERC Information

Members of the Committee

Dr. Catherine Moltzan (Chair), Dr. Kelvin Chan (Vice-Chair), Paul Agbulu, Dr. Phillip Blanchette, Dr. Matthew Cheung, Dr. Michael Crump, Annette Cyr, Dr. Jennifer Fishman, Dr. Jason Hart, Terry Hawrysh, Dr. Yoo-Joung Ko, Dr. Aly-Khan Lalani, Amy Peasgood, Dr. Anca Prica, Dr. Michael Raphael, Dr. Adam Raymakers, Dr. Patricia Tang, Dr. Pierre Villeneuve, and Danica Wasney.

Meeting date: November 12, 2025

Regrets: Four expert committee members did not attend.

Conflicts of interest: None