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CADTH Reimbursement Recommendation
CADTH recommends that public drug plans reimburse Keytruda for the treatment of locally advanced unresectable or metastatic biliary tract carcinoma (BTC) if certain conditions are met.
Keytruda in combination with gemcitabine-based chemotherapy should only be covered to treat patients with locally advanced unresectable or metastatic BTC who have not received prior treatment or who have completed treatment with nongemcitabine-based neoadjuvant or adjuvant therapy more than 6 months ago. Patients receiving Keytruda should be in relatively good health (i.e., have a good performance status, as determined by a specialist).
Keytruda should only be reimbursed if it is used in combination with gemcitabine-based chemotherapy if prescribed by specialists with experience in managing BTC and if the cost of Keytruda does not exceed the cost of durvalumab. Keytruda should not be reimbursed if it is used to treat patients with ampulla of Vater cancer.
Biliary tract cancers are rare cancers that occur in the bile duct system, which includes the bile ducts within the liver and outside of the liver, as well as in the gallbladder. There will be 1,263 new cases of locally advanced unresectable or metastatic BTC diagnosed in Canada in 2025. The length of survival for patients living in Canada with unresectable BTC is approximately 6 to 12 months.
Limited currently available treatment options are identified as a significant unmet need for patients with advanced BTC. New, life-extending treatments that improve quality of life are desired.
Treatment with Keytruda is expected to cost $9,034.30 for the first 8 of the 21-day cycles and $9,018.70 for every cycle after that.
The pCODR Expert Review Committee (pERC) recommends that pembrolizumab in combination with gemcitabine-based chemotherapy be reimbursed for the treatment of adult patients with locally advanced unresectable or metastatic BTC only if the conditions listed in Table 1 are met.
One international, double-blind, randomized, phase III study (KEYNOTE-966, N = 1,069) consisting of patients with locally advanced, unresectable or metastatic BTC who are treatment naive in this setting demonstrated that treatment with pembrolizumab plus gemcitabine and cisplatin (hereafter referred to as pembrolizumab plus chemotherapy) likely results in a clinically significant increase in the probability of overall survival (OS) compared to placebo plus gemcitabine and cisplatin (hereafter referred to as placebo plus chemotherapy). The median OS was 12.7 months (95% confidence interval [CI], 11.5 to 13.6) in the pembrolizumab plus chemotherapy group versus 10.9 months (95% CI, 9.9 to 11.6) in the placebo plus chemotherapy group with a hazard ratio (HR) of 0.83 (95% CI, 0.72 to 0.95). The between-group differences in the Kaplan-Meier (KM)-estimated OS rates at 12 months and 24 months were 7.5% (95% CI, 1.6 to 13.4) and 6.8% (95% CI, 1.7 to 11.9), respectively, and therefore demonstrated a survival advantage with pembrolizumab plus chemotherapy. Assessment of health-related quality of life (HRQoL) suggested that adding pembrolizumab to chemotherapy may not result in any clinically significant difference compared to chemotherapy alone; however, the evidence had low certainty due to the large amount of missing data in the HRQoL assessment.
Patients and clinicians highlighted the need for accessible treatments that prolong life, alleviate symptoms, maintain patients’ quality of life, and allow for convenient therapy administration. Given the totality of the evidence, pERC concluded that pembrolizumab added to gemcitabine-based chemotherapy meets some of the needs identified by patients, including improvements in survival (albeit modest), similar toxicity profile to chemotherapy alone, and maintaining HRQoL.
The sponsor-submitted network meta-analysis (NMA) results were insufficient to conclude that treatment with pembrolizumab plus chemotherapy differs from durvalumab plus chemotherapy in terms of efficacy or harm. At the sponsor-submitted price for pembrolizumab and publicly listed price for durvalumab, pembrolizumab (using a weight-based dosing or fixed dose for pembrolizumab) was less costly than durvalumab. Assuming pembrolizumab has similar efficacy as durvalumab, the total drug cost per patient throughout treatment with pembrolizumab should not exceed the total drug cost of therapy with durvalumab.
Reimbursement Conditions and Reasons.
BTC is a heterogeneous group of tumours originating in the biliary tree (cholangiocarcinoma) or the gallbladder and cystic duct (gallbladder cancer). Patients with early-stage BTC are usually asymptomatic; therefore most patients (60% to 85%) are diagnosed at the locally advanced unresectable or metastatic stages. Common symptoms of BTCs are jaundice, abdominal discomfort, malaise, hepatomegaly, weight loss, palpable abdominal mass, fever, night sweats, pruritis, dark urine, or clay coloured or light-coloured greasy stools. BTCs are rare and represent less than 1% of all cancers globally. BTCs are aggressive, and high mortality rates are reported in patients with BTCs. Data from Canada support that BTCs are a rare group of malignancies with poor prognosis. BTC comprises less than 0.5% of all cancer diagnoses annually in Canada. It was estimated that in 2025, there will be 1,403 new cases of total BTC and 1,263 new cases of locally advanced unresectable or metastatic BTC. The median survival for patients living in Canada with unresectable BTC is approximately 6 to 12 months.
While chemotherapy, mainly with gemcitabine plus cisplatin, was the first-line standard of care for patients with unresectable locally advanced or metastatic BTC over a decade ago, the combination of a programmed cell death protein ligand 1 (PD-L1) checkpoint inhibitor (durvalumab) and chemotherapy has been introduced in recent years, and an improvement in OS with durvalumab plus chemotherapy compared to chemotherapy alone has been demonstrated in a phase III randomized controlled trial (RCT). Durvalumab, in combination with gemcitabine-based chemotherapy, is the standard of care and is in widespread use throughout Canada for this particular patient population. Pembrolizumab is a high-affinity antibody against programmed cell death protein 1 (PD-1). By inhibiting the PD-1 receptor from binding to its ligands, pembrolizumab reactivates tumour-specific cytotoxic T lymphocytes in the tumour microenvironment. In Canada, pembrolizumab has been issued market authorization to treat various types of cancers. On April 12, 2024, pembrolizumab in combination with gemcitabine-based chemotherapy (herein referred to as pembrolizumab plus chemotherapy) was approved by Health Canada for the treatment of locally advanced, unresectable or metastatic BTC. The sponsor’s reimbursement request is aligned with the Health Canada–approved indication. Pembrolizumab is available as a single-use vial of 100 mg pembrolizumab/4 mL (25 mg/mL) and is administered as an IV infusion over 30 minutes in combination with chemotherapy. The recommended dose of pembrolizumab for BTC treatment is either 200 mg every 3 weeks or 400 mg every 6 weeks (as IV infusion) until disease progression, unacceptable toxicity or up to 24 months or 35 doses for 200 mg or 18 doses for 400 mg, whichever is longer, in patients without disease progression.
To make its recommendation, the committee considered the following information:
One patient group, CCRAN, provided input to the review of pembrolizumab used in combination with chemotherapy for BTC. The CCRAN is a national not-for-profit patient advocacy group that collected inputs from patients and caregivers through a survey between October 20 and December 1, 2023, in collaboration with the CCSN and Gastrointestinal (GI) Society. The CCRAN also contacted the Cholangiocarcinoma Foundation, a US-based patient advocacy group dedicated to supporting patients with cholangiocarcinoma, to obtain additional patient input for this disease via telephone interviews, emails or social media blasts. In total, 4 patients and 4 caregivers provided feedback on their experience of BTC and the treatments. Among them, 5 had experience with pembrolizumab, which was given without chemotherapy, following previous chemotherapy, or in combination with chemotherapy. The number of cycles of pembrolizumab that these patients had received ranged from 2 to 40. Three patients or caregivers received chemotherapy but did not report experience with pembrolizumab.
Based on the patient input, inoperable or metastatic BTC and the currently available treatments significantly negatively impact patients' physical and psychosocial well-being, affecting their everyday life, work and family. The patients often face significant financial difficulties. According to the patients who had received treatment with pembrolizumab, improved cancer-induced symptoms, fewer side effects, improved quality of life and shorter infusion time were reported compared to other treatments.
The patient group input stated that the significant unmet need for patients with metastatic BTC is limited to currently available treatment options in this patient population. Important patient outcomes included improved quality of life, delayed onset of symptoms, reduced side effects compared to the current treatments, and prolonged overall and progression-free survival. The respondents stated that the introduction of novel, more effective, better tolerated and easily administered targeted therapies with equitable access is of paramount importance, particularly in the first-line setting.
The clinical experts indicated that for patients with locally advanced unresectable or metastatic BTC, the most important goals of treatment are to prolong life, delay disease progression, alleviate symptoms and maintain patients’ quality of life. The experts identified these unmet needs associated with the current treatments for advanced BTC: curative therapies are lacking and there are no biomarkers that can help with patient selection.
The clinical experts indicated that currently, durvalumab, in combination with chemotherapy, is widely used in the treatment of advanced BTC, and pembrolizumab will be the second immune checkpoint inhibitor to be used along with chemotherapy for these patients. The experts also noted that pembrolizumab would be used as a first-line treatment, and it is inappropriate to recommend that patients try other therapies before initiating pembrolizumab. Furthermore, the experts suggested that after a maximum of 8 cycles of combination therapy, treatment with pembrolizumab could be continued with or without gemcitabine.
The clinical experts noted that since no biomarkers have been identified in selecting patients suitable for the combination regimen, all patients with advanced BTC should be eligible for pembrolizumab plus chemotherapy if this is not contraindicated in these patients. For example, patients with good performance status and without comorbidities that may preclude them from receiving chemotherapy (e.g., cisplatin or carboplatin plus gemcitabine) are eligible. The experts noted that in clinical practice, patients on the treatments for advanced BTC would have regular imaging scans, such as CTs, to monitor their responses to the treatments. Other assessments include patients’ functional status (e.g., ECOG performance status) and disease status. Usually, these assessments are reviewed every 2 to 3 months for patients with advanced BTC. The treating physicians consistently adopt this practice.
According to the clinical experts consulted by CADTH, treatment with a combination of pembrolizumab and chemotherapy will be discontinued if disease progression is detected based on the results of an imaging scan or if the patients experience any intolerable adverse effects related to the treatment.
The clinical experts noted that, in general, patients should be treated by a medical oncologist knowledgeable about BTC management, and they should receive treatment in any setting, such as a community or academic centre.
One clinician group provided input for reviewing pembrolizumab in combination with chemotherapy: Ontario Health (Cancer Care Ontario) (OH-CCO) Gastrointestinal Cancer Drug Advisory Committee.
In general, the clinician group input was consistent with the feedback provided by the clinical experts consulted by CADTH for this review. CCO noted that the standard of care for patients with advanced BTC is gemcitabine plus cisplatin and gemcitabine plus carboplatin, and the treatment goals are prolonged life, delayed disease progression, and improved quality of life. CCO added that since there is only 1 available regimen with a poor duration of response, new regimens are required.
The clinician group stated that pembrolizumab can be safely added to the first-line chemotherapy, which is well tolerated, and all patients who align with the clinical trial criteria are best suited for the drug under review. The clinician group believes that clinical and/or radiologic progression, as per the discretion of the treating oncologist, determines whether a patient is responding to treatment in clinical practice, and treatment should be discontinued if there is disease progression and toxicity at the discretion of the treating oncologist. Additionally, the appropriate treatment setting would be a hospital (outpatient clinic) and a specialist is required.
The clinical experts consulted by CADTH provided advice on the potential implementation issues raised by the drug programs.
Responses to Questions from the Drug Programs.
One phase III double-blind RCT (KEYNOTE-966, N = 1,069) met the inclusion criteria for the systematic review conducted by the sponsor. This study evaluated the efficacy and safety of the combination of pembrolizumab and chemotherapy versus placebo plus chemotherapy in patients with locally advanced, unresectable or metastatic BTC. Patients were randomized at a 1:1 ratio to either pembrolizumab in combination with gemcitabine and cisplatin (chemotherapy) or placebo in combination with chemotherapy. More specifically, patients randomized to pembrolizumab received pembrolizumab 200 mg by IV infusion once every 3 weeks for a maximum of 35 cycles; both patients randomized to pembrolizumab and placebo received treatment in combination with gemcitabine (1,000 mg/m2 on days 1 and 8 of each cycle every 3 weeks; no maximum duration) and cisplatin (25 mg/m2 by IV infusion on days 1 and 8 of each cycle; maximum duration 8 cycles). The primary efficacy end point in the KEYNOTE-966 study was OS. Other relevant outcomes in this study included PFS, HRQoL measured by the EORTC QLQ-C30 and EORTC QLQ-BIL21 questionnaires, and safety. Overall, the patients’ baseline characteristics were balanced between treatment groups. The trial randomized approximately equal proportions of males and females (n for male = 552; 51.6%). Most randomized patients were white (n = 524; 49.0%), had a median age of 64.0 years (range: 23 to 85), had ECOG performance status score of 1 (n = 582; 54.4%), and were from a non-Asian region (n = 583; 54.5%). Most patients had metastatic disease (n = 943; 88.2%) with an intrahepatic site of origin (n = 633; 59.2%). Approximately 30% of these patients received prior surgery (n = 319; 29.8%).
The KEYNOTE-966 study met its primary end point at the final analysis (data cut-off [DCO]: December 15, 2022). The results suggested that treatment with pembrolizumab plus chemotherapy may be associated with prolonged OS, compared with treatment with placebo plus chemotherapy: median OS 12.7 months (95% CI, 11.5 to 13.6) versus 10.9 months (95% CI, 9.9 to 11.6). The HR for OS was 0.83 (95% CI, 0.72 to 0.95, P = 0.0034). Although the between-group difference in median OS was 1.8 months, given the poor prognosis in patients with advanced BTC (with a median OS less than 12 months), an improvement of 1.8 months in median survival is considered a clinically meaningful benefit, according to the clinical experts consulted by CADTH. The between-group differences in the Kaplan-Meier (KM)-estimated OS rates at 6, 12, 18, and 24 months were 7.0% (95% CI, 2.0 to 12.0), 7.5% (95% CI, 1.6 to 13.4), 5.0% (95% CI, −0.5 to 10.5), and 6.8% (95% CI, 1.7 to 11.9), respectively. These estimates were affected by imprecision; the 95% CIs included the potential for trivial effects, based on a threshold for a clinically important between-group difference of 5% as informed by the clinical experts consulted by CADTH. Results of prespecified subgroup analyses based on various patient baseline characteristics were consistent with that in the overall population.
PFS measured with RECIST 1.1 was 1 of the key secondary end points in the KEYNOTE-966 study. At DCO of December 15, 2021, the median PFS was 6.5 months (95% CI, 5.7 to 6.9) with pembrolizumab plus chemotherapy and 5.6 months (95% CI, 5.1 to 6.6) with placebo plus chemotherapy. According to the multiplicity scheme, the corresponding HR was 0.86 (95% CI, 0.75 to 1.00), P = 0.0225, which did not meet the prespecified efficacy boundary for a statistically significant PFS benefit for pembrolizumab plus chemotherapy. In the analysis of PFS, the proportional hazards assumption for PFS was formally tested and visually examined to ensure its validity on PFS. No violation of this assumption was found. The between-group difference in KM-estimated PFS rates were 6.2% (95% CI 0, to 12.4), 5.7% (95% CI, −0.5 to 11.9), 5.6% (95% CI, −0.4 to 11.6), 6.3% (95% CI, 0.2 to 12.4), and 3.5% (95% CI, −2.8 to 9.8) for 6, 9, 12, 15 and 18 months, respectively. At 6 months of follow-up, the results showed that pembrolizumab plus chemotherapy may increase the KM-estimated probability of PFS when compared with placebo plus chemotherapy; however, the clinical importance of the increase (6.2%) is uncertain, and the 95% CI included the possibility of no difference between treatments. At 18 months, the evidence was very uncertain about the effect of pembrolizumab plus chemotherapy when compared with placebo plus chemotherapy on the KM-estimated probability of PFS (3.5%), owing to imprecision (the confidence interval included the potential that either treatment could be favoured) and indirectness (due to uncertainty in the adequacy of RECIST 1.1 to measure PFS). Although PFS is typically considered a surrogate for OS in oncology trials, assessing PFS in patients with BTC is complex and may not accurately reflect the PFS benefit gained in patients with BTC.
HRQoL was measured using the EORTC QLQ-C30 and EORTC QLQ-BIL21 questionnaires, the latter of which is specific to patients with CCA and GBC. HRQoL measures were included as exploratory outcomes in the KEYNOTE-966 study. At week 18, approximately 60% of the patients completed the assessment and contributed to the analysis of HRQoL data. As such, the results are at risk of bias due to missing outcomes data. At week 18, the between-group differences in the least squares mean (LSM) changes from baseline in the EORTC QLQ-C30 Global health status (GHS)/QoL, Physical Functioning, and Role Functioning subscale scores were 0.04 (95% CI, −2.52 to 2.60, P = 0.9773), 1.24 (95% CI, −1.42 to 3.90, P = 0.3596), and 2.68 (95% CI, −0.76 to 6.11, P = 0.1264), respectively. The difference in the LSM changes from baseline in the EORTC QLQ-BIL21 Jaundice and Pain subscale scores were 0.26 (95% CI, −1.35 to 1.87, P = 0.7535) and −1.87 (95% CI, −4.26 to 0.53, P = 0.1265), respectively. Based on the between-group minimally important differences (MIDs) for these 2 instruments (EORTC QLQ-C30: ranged from 5 to 10 points for most scales; EORTC QLQ-BIL21: MID not identified for patients with BTC, however it can be extrapolated from other cancer types), HRQoL results suggested that compared to placebo plus chemotherapy, adding pembrolizumab to chemotherapy did may not result in any clinically important difference in the subscale scores for Global health status, Physical Functioning and Role Functioning in EORTC QLQ-C30, and the subscale scores for Jaundice and Pain in EORTC QLQ-BIL21.
The proportion of patients experiencing 1 or more AEs in KEYNOTE-966 was well balanced between the 2 treatment groups, which suggested that adding pembrolizumab to existing chemotherapy is not associated with added risk of adverse events: 99.1% versus 99.6% for any AEs, 52.2% versus 49.3% for SAEs, and 26.1% versus 22.8% for treatment discontinuation due to AEs, for the comparisons between pembrolizumab plus chemotherapy and placebo plus chemotherapy. For patients treated with pembrolizumab, commonly reported any AEs were neutrophil count decreased (62.4%), anemia (61.1%), nausea (44.0%), platelet count decreased (39.9%), fatigue (35.3%) and constipation (35.2%), and for patients treated with placebo, commonly reported any AEs included decreased neutrophil count (61.2%), anemia (58.6%), nausea (46.1%), decreased platelet count (39.7%), fatigue (32.2%) and constipation (35.6%). Commonly reported SAEs were cholangitis (5.9%), pyrexia (5.7%), platelet count decreased (3.6%), biliary tract infection (3.2%), anemia (2.5%), sepsis (2.5%), biliary obstruction (2.3%), neutrophil count decreased (2.1%), and pulmonary embolism (2.1%) in patients treated with pembrolizumab, and were cholangitis (4.5%), biliary tract infection (3.4%), sepsis (3.0%), biliary obstruction (3.0%), ascites (2.4%), pyrexia (2.2%), and liver abscess (2.1%) in patients treated with placebo. The most common reasons for treatment discontinuation due to AEs were decreased neutrophil count (3.6%) and decreased platelet count (3.6%) in patients treated with pembrolizumab, and were neutrophil count decreased (3.0%) in patients treated with placebo.
The proportion of patients with AEs resulting in death was 5.9% (31 patients) in the pembrolizumab plus chemotherapy group and 9.2% (49 patients) in the placebo plus chemotherapy group. Patients in the pembrolizumab plus chemotherapy group reported more AEs of particular interest compared to those in the comparator group, 22.1% versus 12.9%. For the immune-mediated AEs (immune-mediated enterocolitis, hepatitis or lung disease), although it did not appear that pembrolizumab plus chemotherapy resulted in clinically important increases in these events based on a threshold for a clinically important between-group difference of 5 to 10% as informed by the clinical experts consulted by CADTH, few events were reported in the KEYNOTE-966 study, which adds uncertainty to these results. No unusual safety signals were observed for the treatment of pembrolizumab plus chemotherapy. The frequency, type, and severity of harms were consistent with pembrolizumab monotherapy and the harms were not exacerbated by combining pembrolizumab with chemotherapy. According to the clinical experts consulted by CADTH, the AEs observed in the KEYNOTE-966 study are manageable in clinical practice.
In the KEYNOTE-966 study, patients’ baseline demographic and disease characteristics were generally balanced between the 2 treatment groups. However, patients in the pembrolizumab plus chemotherapy group performed relatively better than those in the placebo plus chemotherapy group. This imbalance is likely attributed to chance and does not introduce bias. The clinical experts consulted by CADTH noted that this imbalance would not significantly impact result interpretation.
A multiplicity testing procedure was applied to OS, PFS and overall response rate to control for the type I error rate in the study and across interim analyses. However, other efficacy outcomes were analyzed without multiplicity adjustment, for example, HRQoL assessment using the EORTC QLQ-C30 and EORTC QLQ-BIL21. Nevertheless, there were no statistically significant results in any relevant domains.
HRQoL was assessed using disease-specific instruments, and 1 was specifically designed for patients with BTC. A MID specific for patients with BTC was not identified from the literature; however, a range of potential between-group MIDs was established based on clinical trials of 9 different cancer types and may be used to determine the clinical relevance of the study findings for HRQoL. On the other hand, the completion rates of these 2 questionnaires were approximately 60% in the 2 treatment groups. As such, the risk of bias due to missing outcomes data and its impact on study findings is uncertain.
Based on feedback from the clinical experts consulted by CADTH, the eligibility criteria and baseline characteristics of patients randomized in the KEYNOTE-966 study generally reflected a study population that was consistent with the patients in clinical practice in Canada that would receive combination therapy of pembrolizumab plus chemotherapy. However, the study population may be somewhat healthier. The clinical experts noted that the study results from KEYNOTE-966 could be generalized to patients with advanced BTC in Canada who would be treated with pembrolizumab plus chemotherapy.
For pivotal studies and RCTs identified in the sponsor’s systematic review, GRADE was used to assess the certainty of the evidence for outcomes considered most relevant to inform CADTH’s expert committee deliberations. A final certainty rating was determined as outlined by the GRADE Working Group.
Following the GRADE approach, evidence from RCTs started as high-certainty evidence. It could be rated down for concerns related to study limitations (which refer to internal validity or risk of bias), inconsistency across studies, indirectness, imprecision of effects, and publication bias.
When possible, certainty was rated in the context of an important (nontrivial) treatment effect; if this was not possible, certainty was rated in the context of the presence of any treatment effect (i.e., the clinical importance is unclear). In all cases, the target of the certainty of evidence assessment was based on the point estimate and where it was located relative to the threshold for a clinically important effect (when a threshold was available) or to the null. The threshold for a clinically important effect was 5% to 10% for OS (as informed by the clinical experts consulted by CADTH) and null for PFS (due to uncertainties in the measurement and interpretation of the outcome). The threshold for a clinically important effect for the EORTC QLQ-C30 and EORTC QLQ-BIL21 scores was set according to the presence or absence of an important impact based on thresholds identified in the literature. The certainty of the evidence was summarized narratively for some harm events (e.g., immune-mediated AEs) due to the unavailability of the absolute difference in effects.
The selection of outcomes for the GRADE assessment was based on the sponsor’s Summary of Clinical Evidence, consultation with clinical experts, and input received from patient and clinician groups and public drug plans. The following list of outcomes was finalized in consultation with expert committee members:
Table 3 presents the GRADE summary of findings for pembrolizumab in combination with chemotherapy versus placebo in combination with chemotherapy in the study population.
Summary of Findings for Pembrolizumab in Combination with Chemotherapy Versus Placebo in Combination with Chemotherapy for Patients with Locally Advanced Unresectable or Metastatic BTC.
Summary of Economic Information.
CADTH identified the following key limitations with the sponsor’s analysis: relevant comparators were omitted, treatment costs are uncertain, allocating market share to clinical trials is not appropriate, the market uptake of pembrolizumab plus chemotherapy is uncertain, the budget impact of patients diagnosed in years 1 to 3 is not fully captured, and poor modelling practices were employed.
CADTH reanalyses assumed pembrolizumab is administered with weight-based dosing, assumed gemcitabine is administered up to a maximum of 8 cycles when used in combination with pembrolizumab or durvalumab, aligned ToT for the durvalumab plus chemotherapy regimen with CADTH’s revisions made to the cost-minimization analysis, assumed no vial wastage, set RDI to 100% for all treatments, and set the clinical trial market share to 0%.
The CADTH base case reflects an assumption of future practice (i.e., if durvalumab is reimbursed and becomes the standard of care for most patients). Under this assumption, the budget impact of reimbursing pembrolizumab for use by adult patients with locally advanced unresectable or metastatic BTC, in combination with gemcitabine and cisplatin, is expected to result in cost savings of $1,797,999 in year 1, $7,680,385 in year 2, and $10,831,246 in year 3, for a 3-year total of $20,309,629. CADTH conducted an exploratory analysis to determine the budget impact of reimbursing pembrolizumab based on currently available comparators (i.e., chemotherapy alone). Based on current practices, pembrolizumab is expected to result in an added cost of approximately $95,024,704 over 3-years. Should the uptake of pembrolizumab, the availability or the price of durvalumab paid by participating plans differ from the CADTH base case, the 3-year budget impact could range between a cost savings of $20,309,629 and an added cost of $95,024,704.
The estimated budget impact is highly sensitive to the price, availability, and uptake of durvalumab. If durvalumab negotiations were concluded with price reductions above 43%, pembrolizumab would no longer be cost-saving.
Dr. Maureen Trudeau (Chair), Mr. Daryl Bell, Dr. Philip Blanchette, Dr. Kelvin Chan, Dr. Matthew Cheung, Dr. Michael Crump, Dr. Jennifer Fishman, Mr. Terry Hawrysh, Dr. Yoo-Joung Ko, Dr. Christian Kollmannsberger, Dr. Catherine Moltzan, Ms. Amy Peasgood, Dr. Anca Prica, Dr. Adam Raymakers, Dr. Patricia Tang, Dr. Marianne Taylor, and Dr. W. Dominika Wranik.
Meeting date: May 8, 2024
Regrets: One expert committee member did not attend.
Conflicts of interest: One expert committee member did not participate due to conflict of interest considerations.
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Indication: In combination with gemcitabine-based chemotherapy for the treatment of adult patients with locally advanced unresectable or metastatic biliary tract carcinoma.
Sponsor: Merck Canada Inc.
Final recommendation: Reimburse with conditions
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