First-line Nivolumab Plus Ipilimumab vs Sunitinib for Metastatic Renal Cell Carcinoma: A Cost-effectiveness Analysis

Abstract

Importance: Recently, 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.

Objective: To 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 participants: A 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 measures: Life-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.

Results: Nivolumab 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 relevance: In 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.

Figure 1.. The Results of Univariable Sensitivity Analysis

This diagram shows incremental cost-effectiveness ratio (ICER) of nivolumab plus ipilimumab (IN) vs sunitinib for different model input parameters. The dotted line intersecting the light and dark blue bars represents the ICER of $108 363 per quality-adjusted life-year (QALY) from the base case results. OS indicates overall survival; PFS, progression-free survival; PPE, palmar-plantar erythrodysesthesia.

Figure 2.. The Cost-effectiveness Acceptability Curve

Results of the probabilistic sensitivity analyses based on 10 000 Monte Carlo simulations, which involves sampling model variable values from distributions imposed on variables to indicate uncertainty about whether nivolumab plus ipilimumab are cost-effective at different willingness-to-pay thresholds. For example, nivolumab plus ipilimumab was found to be cost-effective in 80.2% at a willingness-to-pay threshold of $150 000 per QALY. QALY indicates quality-adjusted life-year.