Cost-Effectiveness of Nivolumab Plus Cabozantinib Versus Sunitinib as a First-Line Treatment for Advanced Renal Cell Carcinoma in the United States.
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SUBMITTER: Li S
PROVIDER: S-EPMC8711761 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundThe efficacy and safety of nivolumab plus cabozantinib as compared with those of sunitinib in the treatment of previously untreated advanced renal-cell carcinoma are not known.MethodsIn this phase 3, randomized, open-label trial, we randomly assigned adults with previously untreated clear-cell, advanced renal-cell carcinoma to receive either nivolumab (240 mg every 2 weeks) plus cabozantinib (40 mg once daily) or sunitinib (50 mg once daily for 4 weeks of each 6-week cycle). The primary end point was progression-free survival, as determined by blinded independent central review. Secondary end points included overall survival, objective response as determined by independent review, and safety. Health-related quality of life was an exploratory end point.ResultsOverall, 651 patients were assigned to receive nivolumab plus cabozantinib (323 patients) or sunitinib (328 patients). At a median follow-up of 18.1 months for overall survival, the median progression-free survival was 16.6 months (95% confidence interval [CI], 12.5 to 24.9) with nivolumab plus cabozantinib and 8.3 months (95% CI, 7.0 to 9.7) with sunitinib (hazard ratio for disease progression or death, 0.51; 95% CI, 0.41 to 0.64; P<0.001). The probability of overall survival at 12 months was 85.7% (95% CI, 81.3 to 89.1) with nivolumab plus cabozantinib and 75.6% (95% CI, 70.5 to 80.0) with sunitinib (hazard ratio for death, 0.60; 98.89% CI, 0.40 to 0.89; P = 0.001). An objective response occurred in 55.7% of the patients receiving nivolumab plus cabozantinib and in 27.1% of those receiving sunitinib (P<0.001). Efficacy benefits with nivolumab plus cabozantinib were consistent across subgroups. Adverse events of any cause of grade 3 or higher occurred in 75.3% of the 320 patients receiving nivolumab plus cabozantinib and in 70.6% of the 320 patients receiving sunitinib. Overall, 19.7% of the patients in the combination group discontinued at least one of the trial drugs owing to adverse events, and 5.6% discontinued both. Patients reported better health-related quality of life with nivolumab plus cabozantinib than with sunitinib.ConclusionsNivolumab plus cabozantinib had significant benefits over sunitinib with respect to progression-free survival, overall survival, and likelihood of response in patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol Myers Squibb and others; CheckMate 9ER ClinicalTrials.gov number, NCT03141177.).
| S-EPMC8436591 | biostudies-literature
Project description:ImportanceRecently, new drugs have been approved for the first-line treatment of metastatic renal cell carcinoma (mRCC). Nivolumab plus ipilimumab significantly increases overall survival for intermediate- and poor-risk patients with mRCC. However, considering the high cost of nivolumab plus ipilimumab, there is a need to assess its value by considering both efficacy and cost.ObjectiveTo evaluate the cost-effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line setting for intermediate- and poor-risk patients with mRCC from the US payer perspective.Design, setting, and participantsA Markov model was developed to compare the lifetime cost and effectiveness of nivolumab plus ipilimumab vs sunitinib in the first-line treatment of mRCC using outcomes data from the CheckMate 214 phase 3 randomized clinical trial, which included 1096 patients with mRCC (median age, 62 years) and compared nivolumab plus ipilimumab vs sunitinib as first-line treatment of mRCC. In the analysis, patients were modeled to receive sunitinib or nivolumab plus ipilimumab for 4 doses followed by nivolumab monotherapy.Main outcomes and measuresLife-years, quality-adjusted life-years (QALYs), and lifetime costs were estimated, at a willingness-to-pay threshold of $100 000 to $150 000 per QALY. Univariable, 2-way, and probabilistic sensitivity analyses were performed to evaluate the model uncertainty. Additional subgroup analyses were performed.ResultsNivolumab plus ipilimumab provided an additional 0.96 QALYs, at a cost of $108 363 per QALY. Sensitivity analyses found the results to be most sensitive to overall survival hazard ratio (0.63; 95% CI, 0.44-0.89) and mean patient weight (70 kg, range, 40-200 kg). Other variables, such as the cost of nivolumab plus ipilimumab (mean, $32 213.44; range, $25 770.75-$38 656.13), utility values for nivolumab plus ipilimumab (mean, 0.82; range, 0.65-0.98), and proportion receiving nivolumab in sunitinib arm (mean, 0.27; range, 0.22-0.32), had a moderate or minor influence on model results. Subgroup analyses demonstrated that nivolumab plus ipilimumab was most cost-effective for patients with programmed cell death 1 ligand 1 expression of at least 1% ($86 390 per QALY).Conclusions and relevanceIn this model, nivolumab plus ipilimumab was estimated to be cost-effective compared with sunitinib for intermediate- and poor-risk patients with mRCC at a willingness-to-pay threshold from $100 000 to $150 000 per QALY.
| S-EPMC6459127 | biostudies-literature
Project description:BACKGROUND:Nivolumab plus ipilimumab improves overall survival and is associated with less toxicity compared with sunitinib in the first-line setting of advanced renal-cell carcinoma (RCC). The current study aimed to assess the cost-effectiveness of nivolumab plus ipilimumab for first-line treatment of advanced RCC from the payer perspectives high- and middle-income regions. METHODS:A decision-analytic model was constructed to evaluate the health and economic outcomes of first-line sunitinib and nivolumab plus ipilimumab treatment associated with advanced RCC. The clinical and utility data were obtained from published reports. The cost data were acquired for the payer perspectives of the United States (US), United Kingdom (UK), and China. Sensitivity analyses were performed to test the uncertainties of the results. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were used. RESULTS:Nivolumab plus ipilimumab gained 0.70-0.76 QALYs compared with sunitinib. Our analysis determined the following ICERs for nivolumab plus ipilimumab over sunitinib in first-line advanced RCC treatment: US $ 85,506 /QALY; UK $ 126,499/QALY; and China $ 4682/QALY. Sensitivity analyses found the model outputs to be most affected for body weight and for the prices of nivolumab, sunitinib and ipilimumab. CONCLUSIONS:Nivolumab plus ipilimumab as first-line treatment could gain more health benefits for advanced RCC in comparison with standard sunitinib, which is considered to be cost-effective in the US and China but not in the UK.
| S-EPMC6247499 | biostudies-literature
Project description:BackgroundCabozantinib was approved by the European Medicines Agency and the Federal Drug Administration as an option for sorafenib-resistant advanced hepatocellular carcinoma, increasing overall survival and progression-free survival compared with placebo. We evaluated the cost-effectiveness of cabozantinib in the second-line setting for patients with an advanced hepatocellular carcinoma from the German statutory health insurance perspective compared with an US scenario using US prices.MethodsA Markov model was developed to compare the costs and effectiveness of cabozantinib with best supportive care in the second-line treatment of advanced hepatocellular carcinoma over a lifetime horizon. Health outcomes were measured in discounted life years and discounted quality-adjusted life years. Survival probabilities were estimated using parametric survival distributions based on CELESTIAL trial data. Utilities were derived from the literature. Costs contained drugs, monitoring and adverse events measured in US Dollars. Model robustness was addressed in univariable, scenario and probabilistic sensitivity analyses.ResultsCabozantinib generated a gain of 0.18 life years (0.15 quality-adjusted life years) compared with best supportive care. The total mean cost per patient was $56,621 for cabozantinib and $2064 for best supportive care in the German model resulting in incremental cost-effectiveness ratios for cabozantinib of $306,778/life year and $375,470/quality-adjusted life year. Using US prices generated costs of $177,496 for cabozantinib and $4630 for best supportive care and incremental cost-effectiveness ratios of $972,049/life year and $1,189,706/quality-adjusted life year.ConclusionsOur analysis established that assuming a willingness-to-pay threshold of $163,371/life year (quality-adjusted life year) for the German model and $188,559/life year (quality-adjusted life year) for the US model, cabozantinib is not cost-effective compared with best supportive care. Sensitivity analyses showed that cabozantinib was not cost-effective in almost all our scenarios.
| S-EPMC7171756 | biostudies-literature
Project description:Background:Compared with the standard of care with sunitinib, avelumab plus axitinib can increase progression-free survival in the first-line of advanced renal cell carcinoma (RCC), but the economic effect of the treatment is unknown. The purpose of the research was to evaluate the cost-effectiveness of the avelumab plus axitinib versus sunitinib in first-line treatment for advanced RCC from the US payer perspective. Methods:A Markov model was developed to evaluate the economic and health outcomes of avelumab plus axitinib vs sunitinib in the first-line setting for advanced RCC. The clinical data were obtained from the JAVELIN Renal 101 Clinical Trials. Deterministic and probabilistic sensitivity analyses were performed to assess uncertainty in the model. Health outcomes were measured in quality-adjusted life-years (QALYs). Results:The incremental cost-effectiveness ratio (ICER) of avelumab plus axitinib compared with sunitinib was $565,232 per QALY, the costs were $884,626 and $669,838, QALYs were 3.67 and 3.29, respectively. Sensitivity analysis demonstrated that differences in utilities in PFS and after progression were the most influential factors within the model. When avelumab was at 30% of the full price or axitinib was at 40% of the full price, avelumab and axitinib were approved to be cost-effective if the WTP threshold was $150,000 per QALY. The subgroup analysis showed the ICER of avelumab plus axitinib compared with sunitinib for the patients with PD-L1-positive tumors was $588,105. Conclusion:Avelumab plus axitinib in the first-line treatment was not cost-effective in comparison with sunitinib when the threshold of willingness to pay (WTP) was $150,000 per QALY.
| S-EPMC7225300 | biostudies-literature
Project description:Purpose: The effectiveness of nivolumab plus ipilimumab for advanced non-small cell lung cancer (NSCLC) has been demonstrated. Decisions have to be made about allocating healthcare resources. Economic evidence could support policy decisions to fund expensive interventions. The current analysis evaluated the cost-effectiveness of nivolumab plus ipilimumab in advanced NSCLC harboring no EGFR or ALK mutations. It is set in the context of the US and China, representing developed and resource-constrained settings, respectively. Patients and Methods: A Markov model consisting of three discrete health states was used to assess the cost-effectiveness of nivolumab plus ipilimumab vs. chemotherapy. The key clinical data were derived from the CheckMate-227 trial, and the cost and health preference data were derived from the literature. Costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs) and incremental net health benefits (INHBs) were calculated for the two strategies. Subgroup, one-way and probabilistic sensitivity analyses were performed. Results: In the United States, nivolumab plus ipilimumab increased by 1.260 QALYs with an additional cost of $95,617 compared with the features of chemotherapy, which led to an ICER of $75,871 per QALY gained. INHB indicated that nivolumab plus ipilimumab treatment had a 99% probability of being cost-effective at the ICER threshold of $100,000/QALY in all subgroups. The results of sensitivity analyses revealed that the model outcomes were robust. In China, the ICER of nivolumab plus ipilimumab vs. chemotherapy was $59,773/QALY, and the INHB was -1.972 QALY at the threshold of $27,351/QALY. Conclusion: Nivolumab plus ipilimumab treatment is a cost-effective option compared with chemotherapy for patients with advanced NSCLC harboring no EGFR or ALK mutations in the United States. However, nivolumab plus ipilimumab is not a preferred option in China.
| S-EPMC8287729 | biostudies-literature
Project description:Background:We evaluated the cost-effectiveness of nivolumab versus everolimus in patients with advanced renal cell carcinoma (RCC) from a US payer perspective. Methods:A partitioned survival model consisting of three health states, progression-free survival (PFS), progressive disease, and death, was developed to evaluate the cost-effectiveness of intravenous nivolumab versus oral everolimus over a lifetime. The proportion of patients in each state was calculated based on parametric distributions fitted to PFS and overall survival (OS) data from CheckMate 025 (N = 821), a large randomized phase 3 trial of nivolumab versus everolimus for advanced RCC. Health state utility data were derived from CheckMate 025 EQ-5D data. Scenario analyses and deterministic and probabilistic sensitivity analyses assessed the impact of uncertainty in model inputs on outcomes. Results:Over a 25-year lifetime horizon, treatment with nivolumab resulted in a gain of 0.64 quality-adjusted life-years (QALYs) versus everolimus. Nivolumab had greater total costs versus everolimus ($US197,089 vs. $US163,902), mainly due to higher acquisition costs. The incremental cost-utility ratio (ICUR), a measure of incremental costs divided by incremental QALYs, was $US51,714 per QALY gained for nivolumab versus everolimus, and an incremental cost-effectiveness ratio was $US44,576 per life-year gained for nivolumab versus everolimus. In sensitivity analyses, average body weight had the greatest impact on the ICUR for nivolumab versus everolimus (base case $US51,714; range $US8863-$US94,566). At a $US150,000 willingness-to-pay (WTP) threshold, nivolumab had a 91.7% probability of being cost-effective versus everolimus. Conclusions:In the United States, at a WTP threshold of $US150,000 per QALY, nivolumab was found to be cost-effective. Key drivers of cost-effectiveness were survival inputs for OS and the average weight of patients; the latter directly affects nivolumab drug acquisition cost.
| S-EPMC5810189 | biostudies-literature
Project description:ImportanceCheckpoint inhibitor combination therapy represents a major advance in the first-line treatment of advanced renal cell carcinoma. Pembrolizumab-axitinib and nivolumab-ipilimumab have become standard of care options after demonstrating clinical efficacy against sunitinib in separate phase 3 trials. The cost-effectiveness of these regimens is unknown.ObjectiveTo evaluate the cost-effectiveness of pembrolizumab-axitinib and nivolumab- ipilimumab in the first-line treatment of advanced renal cell carcinoma.Design, setting, and participantsFor this economic evaluation, a primary microsimulation model was developed and run between August and December 2019. Separate analyses were conducted for an intermediate- and poor-risk patient population (base case) and a favorable-risk population (exploratory analysis) because prognosis is known to differ between risk groups; 100 000 patients with advanced renal cell carcinoma were simulated in each treatment arm. Survival, treatment regimens, and other relevant conditions were based on data from the phase 3 KEYNOTE-426 and CheckMate214 clinical trials. The study perspective was the US health care sector.Main outcomes and measuresAn incremental cost-effectiveness ratio was calculated for each of the 2 analyses and compared with a willingness-to-pay threshold of $100 000 per quality-adjusted life-year (QALY).ResultsPembrolizumab-axitinib was estimated to add 0.60 QALYs compared with nivolumab-ipilimumab in the base case analysis (3.66 vs 3.05 QALYs) and 0.25 QALYs compared with nivolumab-ipilimumab in the exploratory analysis (4.55 vs 4.30 QALYs), and was more costly (base case analysis: $562 927 vs $458 961; exploratory analysis: $589 035 vs $470 403). The incremental cost-effectiveness ratio was $172 532 per QALY in the base case analysis and $468 682 per QALY in the exploratory analysis. One-way sensitivity analyses revealed that the base case model was most sensitive to first-line drug prices (incremental cost-effectiveness ratio at upper limit of nivolumab price and lower limits of axitinib and pembrolizumab prices: $89 983, $102 287, and $114 943 per QALY, respectively). The exploratory analysis model was most sensitive to overall survival rates (incremental cost-effectiveness ratio at lower limit of pembrolizumab-axitinib rate and upper limit of nivolumab-ipilimumab rate: $278 644 and $285 684 per QALY, respectively).Conclusions and relevanceThe findings suggest that pembrolizumab-axitinib treatment is associated with greater QALYs compared with nivolumab/ipilimumab treatment in patients with advanced renal cell carcinoma but may not be cost-effective. Price reductions may make the cost of pembrolizumab-axitinib proportional to its clinical value and less financially burdensome to the US health care system.
| S-EPMC7557509 | biostudies-literature
Project description:BACKGROUND:Nivolumab plus ipilimumab produced objective responses in patients with advanced renal-cell carcinoma in a pilot study. This phase 3 trial compared nivolumab plus ipilimumab with sunitinib for previously untreated clear-cell advanced renal-cell carcinoma. METHODS:We randomly assigned adults in a 1:1 ratio to receive either nivolumab (3 mg per kilogram of body weight) plus ipilimumab (1 mg per kilogram) intravenously every 3 weeks for four doses, followed by nivolumab (3 mg per kilogram) every 2 weeks, or sunitinib (50 mg) orally once daily for 4 weeks (6-week cycle). The coprimary end points were overall survival (alpha level, 0.04), objective response rate (alpha level, 0.001), and progression-free survival (alpha level, 0.009) among patients with intermediate or poor prognostic risk. RESULTS:A total of 1096 patients were assigned to receive nivolumab plus ipilimumab (550 patients) or sunitinib (546 patients); 425 and 422, respectively, had intermediate or poor risk. At a median follow-up of 25.2 months in intermediate- and poor-risk patients, the 18-month overall survival rate was 75% (95% confidence interval [CI], 70 to 78) with nivolumab plus ipilimumab and 60% (95% CI, 55 to 65) with sunitinib; the median overall survival was not reached with nivolumab plus ipilimumab versus 26.0 months with sunitinib (hazard ratio for death, 0.63; P<0.001). The objective response rate was 42% versus 27% (P<0.001), and the complete response rate was 9% versus 1%. The median progression-free survival was 11.6 months and 8.4 months, respectively (hazard ratio for disease progression or death, 0.82; P=0.03, not significant per the prespecified 0.009 threshold). Treatment-related adverse events occurred in 509 of 547 patients (93%) in the nivolumab-plus-ipilimumab group and 521 of 535 patients (97%) in the sunitinib group; grade 3 or 4 events occurred in 250 patients (46%) and 335 patients (63%), respectively. Treatment-related adverse events leading to discontinuation occurred in 22% and 12% of the patients in the respective groups. CONCLUSIONS:Overall survival and objective response rates were significantly higher with nivolumab plus ipilimumab than with sunitinib among intermediate- and poor-risk patients with previously untreated advanced renal-cell carcinoma. (Funded by Bristol-Myers Squibb and Ono Pharmaceutical; CheckMate 214 ClinicalTrials.gov number, NCT02231749 .).
| S-EPMC5972549 | biostudies-literature
Project description:BackgroundThe data from the phase III clinical trial KEYNOTE-426 indicated that pembrolizumab plus axitinib compared with sunitinib could generate clinical benefits in patients with previously untreated advanced renal cell carcinoma (RCC). Given the incremental clinical benefits, we examined the potential cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in the first-line setting for patients with advanced RCC from the U.S. payers' perspective.Materials and methodsCost and health outcomes were estimated at a willingness-to-pay (WTP) threshold of $100,000 to $150,000 per quality-adjusted life-year (QALY). One-way and probabilistic sensitivity analyses were performed by varying potentially modifiable parameters, and additional subgroup analyses were performed as well.ResultsUpon our analyses, the total treatment costs in the pembrolizumab plus axitinib and sunitinib groups were $522,796 and $348,424 and the QALYs gained 2.90 and 1.72, respectively. In the base-case analysis, compared with receiving sunitinib, patients with advanced RCC receiving pembrolizumab plus axitinib gained 1.18 more QALYs at an incremental cost-effectiveness ratio of $148,676/QALY. The results of subgroup analyses demonstrated that pembrolizumab plus axitinib was most cost-effective for patients who had one organ with metastasis.ConclusionFirst-line treatment with pembrolizumab plus axitinib, compared with sunitinib, is a cost-effective strategy when the value of WTP is from $100,000 to $150,000 per QALY in patients with advanced RCC. For patients with one-organ metastasis and those in International Metastatic Renal Cell Carcinoma Database Consortium poor risk group, first-line treatment with pembrolizumab plus axitinib is more cost-effective than others.Implications for practiceThis was the first study to examine the cost-effectiveness of pembrolizumab plus axitinib versus sunitinib in advanced renal cell carcinoma (RCC). This study found that first-line treatment with pembrolizumab plus axitinib is a cost-effective strategy when the value of willingness-to-pay is from $100,000 to $150,000 per quality-adjusted life-year in patients with advanced RCC from the U.S. payers' perspective.
| S-EPMC7873332 | biostudies-literature