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:PurposeIn the phase 3 CheckMate 9ER trial, intravenous nivolumab (240 mg every 2 weeks) plus oral cabozantinib (40 mg/day) improved progression-free survival (PFS) versus sunitinib as first-line therapy for advanced renal cell carcinoma (RCC). To support cabozantinib dosing with the combination, this exposure-response analysis characterized the relationship of cabozantinib exposure with clinical endpoints.MethodsDose modification was allowed with cabozantinib (holds and reductions) to manage adverse events (AEs). The population pharmacokinetics analysis was updated and used to generate individual predicted cabozantinib exposure measures. Kaplan-Meier plots and time-to-event Cox proportional hazard (CPH) exposure-response models characterized the relationship of cabozantinib exposure with PFS, dose modifications, and selected AEs.ResultsKaplan-Meier plots showed no clear difference in PFS across cabozantinib exposure quartiles. Cabozantinib exposure did not significantly affect the hazard of PFS in the CPH base model nor in the final model. In contrast, baseline albumin and nivolumab clearance had a significant effect on PFS. There was no significant relationship between cabozantinib clearance and risk of dose modification, but a significant relationship was identified between cabozantinib exposure and Grade ≥ 1 palmar-plantar-erythrodysesthesia and Grade ≥ 3 diarrhea in the exposure-response analysis.ConclusionTo optimize individual cabozantinib exposure, these data support the dose modification strategies in CheckMate 9ER for cabozantinib in patients with advanced RCC when combined with nivolumab.
| S-EPMC9905187 | biostudies-literature
Project description:BackgroundIn the Checkmate9ER trial, first-line treatment with nivolumab combined with cabozantinib (NI + CA) has shown efficacy for advanced renal cell carcinoma. This study aims to evaluate the impact of the health and economic outcomes of NI + CA in China.MethodsClinical efficacy data were derived from pivotal phase III CheckMate 9ER trial. A three-state partitioned survival model was established based on disease progression. Progression-free survival and overall survival of NI + CA vs. sunitinib were fitted with log-logistic and log-normal distributions, respectively. Mixture cure, non-mixture cure, and Royston/Parmar spline models were used to evaluate model robustness. The results derived the computational cost from the Chinese healthcare system perspective. The primary outcomes were quality-adjusted life-years (QALYs), total cost in US dollars, as well as incremental cost-effectiveness ratios (ICERs) at the willingness-to-pay threshold in China. One-way and probabilistic sensitivity analysis were also used to assess the robustness of the model.ResultsIn the base-case analysis result, 0.86 additional QALYs could be obtained in the NI+CA (3.84 QALYs) versus the sunitinib strategy (2.97 QALYs). The ICER of NI+CA compared with the sunitinib strategy was US$292,945 per QALY. The ICER value in the NI+CA strategy was higher than the Chinese willingness-to-pay threshold of US$38,024 per QALY. Although NI+CA can improve long-term patient survival significantly over sunitinib in the treatment of advanced renal cell carcinoma, it is unlikely to be cost-effective due to high cost. The results of the one-way sensitivity analysis showed that drug cost, health utility value at the stage of disease progression, and subsequent treatment proportion had a greater impact on the stability of ICER values.ConclusionsNivolumab combined with cabozantinib can prolong the life of patients with advanced renal cell carcinoma and improve their quality of life, but there is a corresponding increase in medical cost. The NI + CA strategy is unlikely to be considered cost-effective in the treatment of advanced RCC from the perspective of Chinese healthcare system.
| S-EPMC9490003 | biostudies-literature
Project description:BackgroundNivolumab 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.MethodsWe 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.ResultsA 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.ConclusionsOverall 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: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: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:BackgroundIn the primary analysis of CheckMate 9ER, nivolumab plus cabozantinib showed superior progression-free survival, overall survival, and objective response over sunitinib in patients with previously untreated advanced renal cell carcinoma (median follow-up of 18·1 months). Here, we report extended follow-up of overall survival and updated efficacy and safety.MethodsThis open-label, randomised, phase 3 trial was done in 125 hospitals and cancer centres across 18 countries. We included patients aged 18 years or older with previously untreated advanced or metastatic clear-cell renal cell carcinoma, a Karnofsky performance status of 70% or higher, measurable disease according to Response Evaluation Criteria in Solid Tumors version 1.1 assessed by the investigator, any International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic risk category, and available tumour tissue for PD-L1 testing. Patients were randomly assigned (1:1) to nivolumab (240 mg) intravenously every 2 weeks plus cabozantinib (40 mg) orally once daily or sunitinib (50 mg orally) once daily (4 weeks per 6-week cycle). Randomisation, stratified by IMDC risk status, tumour PD-L1 expression, and geographical region, was done by permuted block within each stratum using a block size of four, via an interactive response system. The primary endpoint was progression-free survival by blinded independent central review. Overall survival was a secondary endpoint (reported here as the preplanned final analysis according to the protocol). Efficacy was assessed in all randomly assigned patients; safety was assessed in all patients who received at least one dose of any study drug. This ongoing study, closed to recruitment, is registered with ClinicalTrials.gov, NCT03141177.FindingsBetween Sept 11, 2017, and May 14, 2019, 323 patients were randomly assigned to the nivolumab plus cabozantinib group and 328 to the sunitinib group. With an extended follow-up (data cutoff of June 24, 2021; median 32·9 months [IQR 30·4-35·9]), median overall survival was 37·7 months (95% CI 35·5-not estimable) in the nivolumab plus cabozantinib group and 34·3 months (29·0-not estimable) in the sunitinib group (hazard ratio [HR] 0·70 [95% CI 0·55-0·90], p=0·0043) and updated median progression-free survival was 16·6 months (12·8-19·8) versus 8·3 months (7·0-9·7; HR 0·56 [95% CI 0·46-0·68], p<0·0001). Grade 3-4 treatment-related adverse events occurred in 208 (65%) of 320 patients with nivolumab plus cabozantinib versus 172 (54%) of 320 with sunitinib. The most common grade 3-4 treatment-related adverse events were hypertension (40 [13%] of 320 patients in the nivolumab plus cabozantinib group vs 39 [12%] of 320 in the sunitinib group), palmar-plantar erythrodysaesthesia (25 [8%] vs 26 [8%]), and diarrhoea (22 [7%] vs 15 [5%]). Grade 3-4 treatment-related serious adverse events occurred in 70 (22%) of 320 patients in the nivolumab plus cabozantinib group and 31 (10%) of 320 in the cabozantinib group. One additional treatment-related death occurred with sunitinib (sudden death).InterpretationWith extended follow-up and preplanned final overall survival analysis per protocol, nivolumab plus cabozantinib demonstrated improved efficacy versus sunitinib, further supporting the combination in the first-line treatment of advanced renal cell carcinoma.FundingBristol Myers Squibb and Ono Pharmaceutical.
| S-EPMC10305087 | biostudies-literature
Project description:Background and objectivesNovel immunotherapy-based combination treatments have drastically improved clinical outcomes for previously untreated patients with advanced/metastatic renal cell carcinoma (aRCC). This study aimed to assess the temporal trends in grade 3/4 adverse event (AE) rates and associated costs of nivolumab plus cabozantinib combination therapy versus sunitinib monotherapy in previously untreated patients with aRCC.MethodsIndividual patient data from the CheckMate 9ER trial (nivolumab plus cabozantinib: N = 320; sunitinib: N = 320) were used to calculate the proportion of patients experiencing grade 3/4 AEs. AE unit costs were obtained from the United States (US) 2017 Healthcare Cost and Utilization Project (HCUP) and inflated to 2020 US dollars. Per-patient-per-month (PPPM) all-cause and treatment-related grade 3/4 AE costs over 18-months, temporal trends, and top drivers of AE costs were evaluated in both treatment arms.ResultsOverall, the proportion of patients experiencing grade 3/4 AEs decreased over time, with the highest rates observed in the first 3 months for the nivolumab plus cabozantinib and sunitinib arms. Compared with sunitinib, nivolumab plus cabozantinib was associated with consistently lower average all-cause AE costs PPPM [month 3: $2021 vs. $3097 (p < 0.05); month 6: $1653 vs. $2418 (p < 0.05); month 12: $1450 vs. $1935 (p > 0.05); month 18: $1337 vs. $1755 (p > 0.05)]. Over 18 months, metabolism and nutrition disorders ($244), laboratory abnormalities ($182), and general disorders and administration site conditions ($122) were the costliest all-cause PPPM AE categories in the nivolumab plus cabozantinib arm, and laboratory abnormalities ($443), blood and lymphatic system disorders ($254), and metabolism and nutrition disorders ($177) were the costliest in the sunitinib arm. Trends of treatment-related AE costs were consistent with all-cause AE costs.ConclusionsNivolumab plus cabozantinib was associated with lower costs of grade 3/4 AE management PPPM than sunitinib, which accumulated over the 18-month study period.
| S-EPMC9250488 | biostudies-literature
Project description:Background:We evaluated the cost-effectiveness of nivolumab versus everolimus in patients with advanced renal cell carcinoma (RCC) from a US payer perspective. Methods:A partitioned survival model consisting of three health states, progression-free survival (PFS), progressive disease, and death, was developed to evaluate the cost-effectiveness of intravenous nivolumab versus oral everolimus over a lifetime. The proportion of patients in each state was calculated based on parametric distributions fitted to PFS and overall survival (OS) data from CheckMate 025 (N = 821), a large randomized phase 3 trial of nivolumab versus everolimus for advanced RCC. Health state utility data were derived from CheckMate 025 EQ-5D data. Scenario analyses and deterministic and probabilistic sensitivity analyses assessed the impact of uncertainty in model inputs on outcomes. Results:Over a 25-year lifetime horizon, treatment with nivolumab resulted in a gain of 0.64 quality-adjusted life-years (QALYs) versus everolimus. Nivolumab had greater total costs versus everolimus ($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