An official website of the United States government
NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.
Indication: Cabozantinib, in combination with nivolumab, is indicated for the first-line treatment of adult patients with advanced (not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma
What Is the CADTH Reimbursement Recommendation for Cabometyx in Combination With Opdivo?
CADTH recommends that Cabometyx in combination with Opdivo be reimbursed by public drug plans for the treatment of adults with advanced or metastatic renal cell carcinoma (RCC) who have had no prior systemic therapy for metastatic disease if certain conditions are met.
Which Patients Are Eligible for Coverage?
Cabometyx in combination with Opdivo should be covered in patients aged 18 years and older with RCC that is not amenable to curative surgery or radiation therapy, or has spread to other organs; who have not received prior cancer treatment targeting the entire body for advanced RCC; and who are in relatively good health (i.e., have good performance status). Cabometyx in combination with Opdivo should not be reimbursed to treat patients who have active tumours in the brain or spinal cord from the cancer spreading or active autoimmune disease.
What Are the Conditions for Reimbursement?
Cabometyx in combination with Opdivo should be reimbursed if prescribed by a clinician with expertise in treating RCC in an outpatient oncology clinic or institution and the total drug cost of Cabometyx in combination with Opdivo does not exceed the total drug cost of the lowest-cost alternative combination regimen.
Why Did CADTH Make This Recommendation?
Evidence from a clinical trial demonstrated that people with advanced or metastatic RCC treated with Cabometyx in combination with Opdivo experienced a delay in the spread of cancer and lived longer compared to those who were treated with sunitinib.
Based on CADTH’s assessment of the health economic evidence, Cabometyx in combination with Opdivo does not represent good value to the health care system at the public list price. The committee determined that there is not enough evidence to justify a greater cost for Cabometyx in combination with Opdivo than for alternative combination regimens.
Based on public list prices, Cabometyx in combination with Opdivo is estimated to cost the public drug plans approximately $8 million over the next 3 years.
What Is RCC?
RCC is a cancer that begins from the lining of the kidney tubules, the main function of which is to filter and clean blood. People with advanced or metastatic RCC have cancer that has spread to other organs or body parts, such as the bones, adrenal glands, brain, and liver.
Unmet Needs in RCC
Patients with advanced RCC expressed a need for alternative treatment options that can stop disease progression and improve health outcomes and quality of life.
How Much Does Cabometyx Cost?
Treatment with Cabometyx is expected to cost $8,436 per patient per 28-day cycle and $17,823 per patient per 28-day cycle when in combination with Opdivo.
The CADTH pan-Oncology Drug Review Expert Review Committee (pERC) recommends that cabozantinib plus nivolumab be reimbursed for the treatment of adult patients with advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC who have had no prior systemic therapy for metastatic disease only if the conditions listed in Table 1 are met.
One multicentre, randomized, open-label, phase III trial (CheckMate 9ER, N = 651) demonstrated that treatment with cabozantinib plus nivolumab resulted in added clinical benefit in progression-free survival (PFS), overall survival (OS), and objective response rate (ORR) compared with sunitinib in adults with advanced or metastatic RCC of all International Metastatic RCC Database Consortium (IMDC) risk groups who have not received prior treatment. The hazard ratio (HR) for PFS was 0.51 (95% confidence interval [CI], 0.41 to 0.64), representing a 49% reduction in the risk of PFS with cabozantinib plus nivolumab compared with sunitinib at any particular time point. The HR for OS was 0.60 (98.89% CI, 0.40 to 0.89), representing a 40% reduction in the risk of death with cabozantinib plus nivolumab compared with sunitinib at any particular time point. For ORR, the between-group difference was 28.6% (95% CI, 21.7 to 35.6) and the estimated odds ratio between groups was 3.52 (95% CI, 2.51 to 4.95; P < 0.0001) in favour of cabozantinib plus nivolumab. Although pERC was unable to draw definitive conclusions regarding the effects of cabozantinib plus nivolumab on health-related quality of life (HRQoL) compared to sunitinib due to the absence of formal statistical testing and the open-label design of the trial, they noted that the descriptive assessments suggest HRQoL was maintained with cabozantinib plus nivolumab. Due to limitations of the indirect treatment comparisons, pERC was unable to draw definitive conclusions on the relative efficacy of cabozantinib plus nivolumab compared to other combination therapies currently reimbursed for the treatment of RCC in this patient population in Canada.
Patients indicated that there is a need for additional treatment options that can stop disease progression, improve overall outcomes, and improve HRQoL. pERC concluded that cabozantinib plus nivolumab provides another effective treatment option that delays disease progression, improves OS, and potentially maintains HRQoL, and thus meets some of the needs identified by patients.
At the sponsor-submitted price for cabozantinib and publicly listed price for all other drugs, cabozantinib plus nivolumab was more costly than currently funded comparator regimens. As there is no evidence to suggest cabozantinib plus nivolumab is more effective than other immunotherapy plus tyrosine kinase inhibitor (TKI) or double immunotherapy regimens indicated as first-line treatment of adults with advanced or metastatic RCC, the total drug cost of cabozantinib plus nivolumab should not exceed the total drug cost of the lowest-cost alternative combination regimen.
Reimbursement Conditions and Reasons.
RCC is the most common form of kidney cancer, accounting for approximately 90% of all cases around the world. Approximately 8,100 people in Canada were diagnosed with kidney and renal pelvis cancer in 2022, of which 85% of cases were attributed to RCC. RCCs are further classified into different subtypes based on histology (clear cell, papillary, chromophobe, clear cell papillary, collecting duct, medullary, and unclassified). The clear cell component subtype is the most prevalent form of RCC and represents more than 70% of all RCC cases in practice. More than one-third of cases identified at initial diagnosis have metastatic disease, due to the fact that most patients experience few or no symptoms at earlier stages. Common symptoms consist of flank pain, visible blood in the urine, a noticeable mass in the abdomen, loss of appetite, fatigue, pain, and anemia. Patients who have progressed to an advanced stage of RCC generally face a poor prognosis, with reported 5-year survival rates ranging from 0% to 20% for those with metastatic disease.
Treatment options for untreated advanced clear cell RCC are guided by prognostic risk models, particularly the IMDC risk group classification (i.e., favourable, intermediate, and poor).9 Over 80% of patients with metastatic disease are classified as intermediate and poor risk.10 There is no standard therapy for non–clear cell RCC, and it is generally accepted that patients with non–clear cell histology should be treated similarly to patients with clear cell histology. For patients who fall under the IMDC favourable-risk category, the preferred treatments, according to the Kidney Cancer Research Network of Canada (KCRNC) guidelines, are a combination of immunotherapy and vascular endothelial growth factor receptor (VEGF) TKI.9 These include pembrolizumab plus axitinib, pembrolizumab plus lenvatinib or cabozantinib plus nivolumab, with sunitinib or pazopanib as alternative options for patients who have a contraindication to immunotherapy or who are unable to tolerate combination therapy. For patients who fall under the IMDC intermediate-risk or poor-risk categories, the preferred treatments according to the KCRNC guidelines are ipilimumab plus nivolumab, pembrolizumab plus axitinib, cabozantinib plus nivolumab, or pembrolizumab plus lenvatinib, with sunitinib, pazopanib, or cabozantinib monotherapy as alternative options.9
Cabozantinib is approved by Health Canada for the following indication: in combination with nivolumab, for the first-line treatment of adult patients with advanced (not amenable to curative surgery or radiation therapy) or metastatic RCC. Cabozantinib is a small molecule that inhibits multiple receptor tyrosine kinases implicated in tumour growth and angiogenesis, pathologic bone remodelling, drug resistance, and metastatic progression of cancer. The recommended dose for advanced or metastatic RCC is cabozantinib 40 mg, taken orally once daily, plus nivolumab 240 mg IV every 2 weeks or 480 mg IV every 4 weeks.
To make its recommendation, the committee considered the following information:
The information in this section is a summary of input provided by the patient and clinician groups that responded to CADTH’s call for input and from the clinical expert consulted by CADTH for the purpose of this review.
One patient group, KCC, submitted input for this review. KCC reported that patients in Canada do not have access to cabozantinib plus nivolumab; therefore, the group could not gather information on patients’ feedback or experiences with this therapy. Their submission was based on a survey of 2,213 respondents, of which 139 were from Canada, including 111 (80%) patients diagnosed with kidney cancer.
From the patients’ perspective, there is a need for access to new and effective treatment options that can stop disease progression, control drug resistance, and improve overall outcomes and quality of life. The patient group indicated that cabozantinib plus nivolumab could fill an unmet need in papillary RCC and for patients with brain metastases, where additional treatment options are needed.
The clinical expert noted that the unmet needs of patients with advanced RCC include reducing side effects, particularly having access to less toxic therapies, and that available treatments do not have curative potential. The expert also noted that the available treatments are considered palliative, and that most patients’ disease progresses, and next lines of therapy are sought.
The clinical expert noted that cabozantinib plus nivolumab would compete with other first-line options (i.e., single-drug VEGF TKI, TKI-checkpoint inhibitor, or dual checkpoint inhibitor therapy). The expert also indicated that use of cabozantinib plus nivolumab would challenge the existing treatment paradigm as it is unclear what drugs would be effective as second-line treatment after disease progression.
The clinical expert indicated that those with IMDC intermediate-risk or poor-risk prognoses are best suited for cabozantinib plus nivolumab, while patients with IMDC favourable-risk prognosis remain candidates for a single-drug VEGF TKI. The expert also noted that it is not clear from the available data which patients are most likely to respond, although they indicated that it is probable those with the least disease burden are most likely to respond.
The clinical expert noted that measures of response would include radiologic evidence and symptom assessment, conducted every 8 to 12 weeks. Responses include stability of the known sites of disease without worsening of disease-related symptoms and without intolerable side effects.
The clinical expert noted that progressive disease should be a definitive indication to discontinue treatment as should significant side effects. The clinical expert also indicated that, in their opinion, there is a need to rule out “pseudoprogression,” a common phenomenon that suggests early radiologic progression, by allowing the treatment to continue for at least 1 more assessment time point. The types of side effects that could lead to treatment discontinuation would include severe hypertension, severe diarrhea, severe fatigue, liver dysfunction, and any immune mediated adverse events (IMAEs).
The clinical expert noted that a medical oncologist with experience managing immunotherapy and TKI therapies should be required to diagnose, treat, and monitor patients who might receive cabozantinib plus nivolumab in designated community settings.
Two clinician groups, OH-CCO’s GU DAC and KCRNC, submitted input for this review. Input was provided by 7 clinicians, 3 for OH-CCO and 4 for KCRNC. KCRNC highlighted the need for drug development and increasing clinical trial options for patients with non–clear cell histology, developing biomarkers for predicting response to the treatment, decreasing the attrition of patients, and optimizing treatment for brain metastases. OH-CCO’s GU DAC pointed to the lack of further options for refractory disease. Both clinician groups agreed that patients with any IMDC prognostic risk score who have not had treatment would be potentially eligible for systemic treatment with cabozantinib plus nivolumab. The clinician groups indicated that cabozantinib plus nivolumab would be an additional first-line treatment option for patients with advanced RCC, and this combination therapy could potentially address unmet needs for some patients. Both groups indicated that treatment should be discontinued in the case of disease progression or unacceptable toxicity.
Input was obtained from the drug programs that participate in the CADTH reimbursement review process.
The clinical expert consulted by CADTH provided advice on the potential implementation issues raised by the drug programs (refer to Table 2).
Summary of Drug Plan Input and Clinical Expert Response.
One trial, CheckMate 9ER (N = 651), met the inclusion criteria for the systematic review conducted by the sponsor. The objectives of the CheckMate 9ER trial were to evaluate the efficacy and safety of cabozantinib plus nivolumab versus sunitinib in adults with previously untreated advanced RCC with a clear cell component. Patients had any IMDC prognostic risk score and a Karnofsky performance status score of at least 70 (on a scale from 0 to 100, with lower scores indicating greater disability), and were randomized in a 1:1 ratio stratified by IMDC prognostic risk score, geographic region, and tumour expression of the programmed cell death 1 ligand 1 (PD-L1). Eligible patients were randomized to receive cabozantinib 40 mg, taken orally once daily, plus nivolumab 240 mg IV every 2 weeks or sunitinib 50 mg, taken orally once daily, for 4 weeks, followed by 2 weeks off, per 6-week cycle. The primary outcome was PFS assessed by Blinded Independent Central Review (BICR) using Response Evaluation Criteria in Solid Tumours Version 1.1. (RECIST 1.1), and the secondary outcomes were OS, ORR, and safety. HRQoL measured by the Functional Assessment of Cancer Therapy – Kidney Symptom Index (FKSI-19) and 3-Level EQ-5D visual analogue scale (EQ-5D-3L VAS) questionnaires was included as an exploratory outcome. Key baseline patient characteristics were generally balanced between treatment groups. The population was predominately white (82%) and male (71% to 77%), with an approximate mean age of 60 years. Most patients had a Karnofsky performance status score of 90 or 100 (74% to 80%) and the majority (approximately 57%) had an intermediate-risk IMDC score. A similar proportion of patients in both groups had prior radiotherapy (14%) or nephrectomy (approximately 70%).
In total, 335 PFS events had occurred in both groups by interim analysis 1 (data cut-off of March 30, 2020). At a median follow-up of 18.1 months for OS (range, 10.6 to 30.6), the median PFS was 16.6 months (95% CI, 12.5 to 24.9) with cabozantinib plus nivolumab and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (logrank test P < 0.001), with a between-group HR of 0.51 (95% CI, 0.41 to 0.64). The probability of PFS at 9 months was 68.3% (95% CI, 62.6% to 73.2%) and 47.8% (95% CI, 41.7% to 53.6%), respectively. The findings at the interim analysis 2 extended follow-up (data cut-off of June 24, 2021) were consistent with those of interim analysis 1. The results of the sensitivity analyses were consistent with the primary analysis, and the efficacy results were consistent across IMDC prognostic risk categories (favourable, intermediate, and poor risk).
By interim analysis 1 (data cut-off of March 30, 2020), the median OS was not reached in either group (logrank test P = 0.001). An HR of 0.60 (98.89% CI, 0.40 to 0.89) was estimated. The median follow-up for OS was 18.1 months (range, 10.6 to 30.6). OS rates at 9 months were higher in the cabozantinib plus nivolumab group than in the sunitinib group: 89.9% (95% CI, 86.0% to 92.8%) versus 80.5% (95% CI, 75.7% to 84.4%). The findings at the interim analysis 2 extended follow-up (data cut-off of June 24, 2021) were consistent with those of interim analysis 1.
By interim analysis 1 (data cut-off of March 30, 2020), the ORR in the cabozantinib plus nivolumab group was 55.7% (95% CI, 50.1% to 61.2%) and 27.1% (95% CI, 22.4% to 32.3%) in the sunitinib group, with a between-group difference of 28.6% (95% CI, 21.7% to 35.6%). The estimated odds ratio between groups was 3.52 (95% CI, 2.51 to 4.95; P < 0.0001) in favour of cabozantinib plus nivolumab. The findings at the interim analysis 2 extended follow-up (data cut-off of June 24, 2021) were consistent with those of interim analysis 1.
The exploratory HRQoL outcomes of FKSI-19 total and DRS and EQ-5D-3L VAS scores were assessed at the first interim analysis (data cut-off of March 30, 2020) and were not controlled for multiplicity. Mean changes from baseline through week 91 were generally stable for the cabozantinib plus nivolumab group, whereas patients in the sunitinib group had a trend toward decreased scores, and at times were in excess of the minimum important difference (MID) of 3 points.11 In addition, FKSI-DRS score improved from baseline in patients in the cabozantinib plus nivolumab group, whereas patients in the sunitinib group had a decline from baseline after week 7 through week 91. For EQ-5D-3L VAS, patients in the cabozantinib plus nivolumab group had a trend toward improvement, while patients in the sunitinib group remained relatively stable with a trend toward decline through week 91. The mean changes from baseline in both groups did not meet the MID of 712 through week 91. HRQoL was not assessed at the interim analysis 2 extended follow-up.
At least 1 treatment-emergent adverse event (TEAE) was reported in almost all patients in both treatment groups (99.7% of patients in the cabozantinib plus nivolumab group and 99.1% of patients in the sunitinib group). The most common TEAEs in the nivolumab plus cabozantinib group and sunitinib group were diarrhea (65.3% versus 50%, respectively), palmar-plantar erythrodysesthesia syndrome (40.3% versus 41.9%, respectively), hypertension (38.4% versus 37.5%, respectively), hypothyroidism (36.9% versus 31.6%, respectively), and fatigue (33.8% versus 35.6%, respectively). At least 1 serious adverse event (AE) was reported in 53.1% of patients in the cabozantinib plus nivolumab group and 42.2% of patients in the sunitinib group. The most common serious AE in both groups was malignant neoplasm progression (4.7% and 4.4% in the cabozantinib plus nivolumab and sunitinib groups, respectively). Overall, 37.2% of patients in the cabozantinib plus nivolumab group versus 20.9% in the sunitinib group discontinued treatment due to TEAEs. Deaths were reported in 37.2% of patients in the cabozantinib plus nivolumab group and 45.9% of patients in the sunitinib group. Most deaths were attributed to disease progression in both treatment groups (25.0% with cabozantinib plus nivolumab and 34.7% with sunitinib). Most notable harms occurred in similar percentages of patients in both groups, with hypertension being the most frequently reported notable harm in both study groups (39.7% versus 39.4% in the cabozantinib plus nivolumab and sunitinib groups, respectively). Thrombotic events occurred in 13.4% versus 6.3% of patients treated with cabozantinib plus nivolumab versus sunitinib, respectively. In terms of IMAEs, the cabozantinib plus nivolumab group had a higher incidence compared to the sunitinib group for all IMAEs, with hypothyroidism and/or thyroiditis being the most frequently observed IMAE in the cabozantinib plus nivolumab and sunitinib groups (28.1% and 9.4%, respectively).
CheckMate 9ER was an open-label, phase III, randomized, multicentre trial. The open-label design introduces a potential bias in the assessment of PFS and ORR, and a potential reporting bias of the subjective outcomes of HRQoL and safety. However, this bias was mitigated by use of a BICR for PFS and ORR. Randomization procedures, including stratification by IMDC prognostic risk score, tumour PD-L1 expression, and region, were appropriate and conducted by interactive response technology. In general, the baseline characteristics of the patients appeared balanced between groups, indicating that randomization was successful. To minimize the risk of differential measurement error, the trial performed tumour assessments using RECIST 1.1 criteria and radiographic scans were assessed by BICR. There was low selective reporting bias as the data were analyzed in accordance with the prespecified statistical plan. All interim analyses conducted were planned a priori with appropriately specified alpha spending methods, and secondary outcomes were adjusted for multiplicity. The censoring rules for PFS were prespecified, and sample size and power calculations were based on PFS. All planned outcomes were reported, and the intention-to-treat analysis was conducted for the primary (PFS) and secondary outcomes (OS and ORR). Multiplicity adjustments were not conducted for exploratory outcomes, including the analysis of prespecified subgroups. HRQoL was assessed as an exploratory outcome using the FKSI-DRS and EQ-5D-3L questionnaires. The FKSI-DRS questionnaire has been validated in patients with RCC with evidence of reliability, responsiveness, and a MID. Although the EQ-5D-3L has been widely used in oncology trials in different cancer populations, it has not been validated in patients with advanced RCC.
The population requested for the reimbursement aligns with the Health Canada indication, and the dosing and administration of cabozantinib plus nivolumab was consistent with the Health Canada–approved product monograph. The clinical expert consulted by CADTH considered the eligibility criteria and baseline characteristics of the CheckMate 9ER trial generalizable to adults with advanced RCC with a clear cell component in the Canadian setting. The expert also noted that sunitinib, an approved treatment option for untreated patients with advanced RCC in Canada, was an appropriate comparator. The trial included outcomes that were important to patients and clinicians. The patient group indicated that stopping disease progression and improving overall outcomes and HRQoL are important to them.
No long-term extension studies were submitted by the sponsor.
No additional studies addressing gaps in the pivotal and randomized controlled trial evidence were submitted by the sponsor.
One sponsor-submitted NMA was included in the submission to inform the pharmacoeconomic model and to identify indirect comparisons that fill gaps in the evidence for other first-line treatments of interest for advanced RCC. The objective of the NMA was to indirectly compare the efficacy and safety of cabozantinib plus nivolumab to other relevant comparators, including sunitinib, pazopanib, ipilimumab plus nivolumab, axitinib plus avelumab, axitinib plus pembrolizumab, and lenvatinib plus pembrolizumab, in treatment-naive patients with advanced RCC.
Out of 10 eligible trials, 6 were included in the NMA. The rest were excluded due to a lack of relevant data. In total, 5 different NMA approaches were used to generate estimates for PFS, OS, and AEs. For the purpose of this review, the results of the survival end point meta regression for the prognostic risk NMA, fractional polynomial NMA, and standard NMA for AEs are reported. The survival end point meta regression for the prognostic risk NMA attempted to address some sources of heterogeneity across the studies in the network by including patients in the intermediate-risk and poor-risk categories as a covariate, the fractional polynomial NMA was used to inform the pharmacoeconomic model and attempted to address the violation of the proportional hazards assumption that was identified in most trials, and the standard NMA for AEs was the only NMA approach that reported on safety. The fifth approach (the piecewise exponential NMA) was exploratory and did not attempt to address any additional gaps in the other methods and is therefore not reported in this review.
All the connections within the network were limited to 1 study and the comparisons of interest within the network were limited to indirect estimates only. In general, the estimates across the different NMA approaches varied with wide credible intervals. The survival end point meta regression for the prognostic risk NMA results for PFS favoured cabozantinib plus nivolumab versus the comparators during the observed period from the trial. After 5 years’ predictive time horizon, the results favoured nivolumab plus ipilimumab, followed by avelumab plus axitinib and cabozantinib plus nivolumab. The fractional polynomial NMA results for PFS favoured lenvatinib plus pembrolizumab followed by cabozantinib plus nivolumab during the observed period from the trial. After 5 years’ predictive time horizon, the results favoured nivolumab plus ipilimumab, followed by cabozantinib plus nivolumab. For OS, the survival end point meta regression for the prognostic risk NMA results favoured axitinib plus pembrolizumab and lenvatinib plus pembrolizumab followed by cabozantinib plus nivolumab during the observed trial period. After 10 years’ predictive time horizon, the results favoured ipilimumab plus nivolumab followed by cabozantinib plus nivolumab. The fractional polynomial NMA results for OS favoured lenvatinib plus pembrolizumab, followed by cabozantinib plus nivolumab. After the observed period, the results favoured lenvatinib plus pembrolizumab, followed by axitinib plus pembrolizumab and cabozantinib plus nivolumab. For harms, the results for cabozantinib plus nivolumab were less favourable versus other treatments, with nivolumab plus ipilimumab as most favourable.
The methods used to conduct the systematic literature review were prespecified and appropriate to search databases, select studies, extract data, and assess the quality of the included studies. In total, 5 different NMA approaches were used to generate estimates for PFS, OS, and AEs. However, clear rationale for these approaches was not provided by the sponsor. Out of 10 eligible trials, 6 were included in the NMAs; 4 trials were excluded due to lack of relevant data. The authors noted that the NMAs may have been impacted by these exclusions. Based on quantitative and qualitative assessment, the exchangeability assumption was violated as there were several notable sources of heterogeneity and missing data for potential effect modifiers across the included trials, which further limited the ability to assess heterogeneity across the studies. This included patient histology, disease stage, brain metastases, study drug dosing, and follow-up duration. These sources of heterogeneity were not explored sufficiently in any of the NMA approaches, and none addressed the violation of the exchangeability and proportional hazards assumptions collectively. In addition, risk of bias at the individual study level on effect estimates was not explicitly assessed or discussed. Due to these limitations in the NMA approaches used and uncertainty in their estimates, no definitive conclusions could be drawn on the relative treatment effects of cabozantinib plus nivolumab versus other comparators.
Evidence from 1 phase III open-label randomized controlled trial showed that treatment with cabozantinib plus nivolumab resulted in clinically important improvements in PFS, OS, and ORR compared to sunitinib in adults with previously untreated advanced RCC. These results addressed key treatment outcomes noted as important by both patients and clinicians. For HRQoL, no definitive conclusions can be drawn due to the exploratory nature of the outcomes and open-label design of the trial. Due to limitations of the indirect treatment comparisons, no conclusions can be drawn on the relative efficacy and safety of cabozantinib plus nivolumab compared to other active treatments.
Summary of Economic Evaluation.
CADTH identified the following key limitations with the sponsor’s analysis: the number of patients eligible for first-line systemic therapy was underestimated, the estimated treatment durations were not consistent with those of the pharmacoeconomic evaluation, the allocation of market shares to clinical trials is inappropriate, the modelled population does not represent the full Health Canada indication, the eligible Non-Insured Health Benefits program population was inappropriately calculated, less expensive pricing for the lenvatinib dose used in the model is available, the assumption that ipilimumab plus nivolumab will not be displaced by newer treatment options is inappropriate, and its market share may have been overestimated.
CADTH reanalyses included assuming that patients at intermediate-high to high risk of progression after nephrectomy were originally diagnosed with nonadvanced RCC, assuming treatment duration aligned with PFS, removing clinical trials as a comparator, lowering the cost of lenvatinib to the least expensive option, and assuming that cabozantinib plus nivolumab will also displace ipilimumab plus nivolumab in the intermediate-risk or poor-risk subpopulations. CADTH also made several corrections to the sponsor’s model but was unable to correct the calculation of the eligible Non-Insured Health Benefits program population.
CADTH reanalyses suggest that the reimbursement of cabozantinib plus nivolumab for the first-line treatment of advanced or metastatic clear cell RCC would be associated with a budgetary increase of $1,113,684 in year 1, $2,559,415 in year 2, and $4,938,052 in year 3, for a 3-year incremental budgetary cost of $8,611,151.
Dr. Maureen Trudeau (Chair), Mr. Daryl Bell, Dr. Jennifer Bell, Dr. Matthew Cheung; Dr. Winson Cheung, Dr. Michael Crump, Dr. Leela John, Dr. Christian Kollmannsberger, Mr. Cameron Lane, 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: September 13, 2023
Regrets: None
Conflicts of interest: None
Disclaimer: The information in this document is intended to help Canadian health care decision-makers, health care professionals, health systems leaders, and policy-makers make well-informed decisions and thereby improve the quality of health care services. While patients and others may access this document, the document is made available for informational purposes only and no representations or warranties are made with respect to its fitness for any particular purpose. The information in this document should not be used as a substitute for professional medical advice or as a substitute for the application of clinical judgment in respect of the care of a particular patient or other professional judgment in any decision-making process. The Canadian Agency for Drugs and Technologies in Health (CADTH) does not endorse any information, drugs, therapies, treatments, products, processes, or services.
While care has been taken to ensure that the information prepared by CADTH in this document is accurate, complete, and up-to-date as at the applicable date the material was first published by CADTH, CADTH does not make any guarantees to that effect. CADTH does not guarantee and is not responsible for the quality, currency, propriety, accuracy, or reasonableness of any statements, information, or conclusions contained in any third-party materials used in preparing this document. The views and opinions of third parties published in this document do not necessarily state or reflect those of CADTH.
CADTH is not responsible for any errors, omissions, injury, loss, or damage arising from or relating to the use (or misuse) of any information, statements, or conclusions contained in or implied by the contents of this document or any of the source materials.
This document may contain links to third-party websites. CADTH does not have control over the content of such sites. Use of third-party sites is governed by the third-party website owners’ own terms and conditions set out for such sites. CADTH does not make any guarantee with respect to any information contained on such third-party sites and CADTH is not responsible for any injury, loss, or damage suffered as a result of using such third-party sites. CADTH has no responsibility for the collection, use, and disclosure of personal information by third-party sites.
Subject to the aforementioned limitations, the views expressed herein are those of CADTH and do not necessarily represent the views of Canada’s federal, provincial, or territorial governments or any third-party supplier of information.
This document is prepared and intended for use in the context of the Canadian health care system. The use of this document outside of Canada is done so at the user’s own risk.
This disclaimer and any questions or matters of any nature arising from or relating to the content or use (or misuse) of this document will be governed by and interpreted in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and all proceedings shall be subject to the exclusive jurisdiction of the courts of the Province of Ontario, Canada.
The copyright and other intellectual property rights in this document are owned by CADTH and its licensors. These rights are protected by the Canadian Copyright Act and other national and international laws and agreements. Users are permitted to make copies of this document for noncommercial purposes only, provided it is not modified when reproduced and appropriate credit is given to CADTH and its licensors.
Redactions: Confidential information in this document may be redacted at the request of the sponsor in accordance with the CADTH Drug Reimbursement Review Confidentiality Guidelines.
About CADTH: CADTH is an independent, not-for-profit organization responsible for providing Canada’s health care decision-makers with objective evidence to help make informed decisions about the optimal use of drugs, medical devices, diagnostics, and procedures in our health care system.
Funding: CADTH receives funding from Canada’s federal, provincial, and territorial governments, with the exception of Quebec.
Indication: Cabozantinib, in combination with nivolumab, is indicated for the first-line treatment of adult patients with advanced (not amenable to curative surgery or radiation therapy) or metastatic renal cell carcinoma.
Sponsor: Ipsen Biopharmaceuticals Canada Inc.
Final recommendation: Reimburse with conditions
Copyright © 2023 - Canadian Agency for Drugs and Technologies in Health. Except where otherwise noted, this work is distributed under the terms of a Creative Commons Attribution-NonCommercial- NoDerivatives 4.0 International licence (CC BY-NC-ND).
Your browsing activity is empty.
Activity recording is turned off.
See more...
