OBJECTIVES

: Two checkpoint inhibitor combination therapies – pembrolizumab plus axitinib (axi/pembro) and nivolumab plus ipilimumab (ipi/nivo) – have recently become the standard of care for first-line treatment of advanced clear-cell renal cell carcinoma (aRCC). In the base case of our study, we estimate their relative cost-effectiveness among intermediate or poor risk patients as defined by the International Metastatic RCC Database Consortium (IMDC) risk model.

METHODS

: Using a decision-analytic microsimulation model, we evaluated axi/pembro and ipi/nivo as first-line treatment strategies for aRCC from the US healthcare sector perspective. Incremental cost-effectiveness ratios (ICERs) were calculated separately for the two models and compared to a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY).

Modeling of progression-free and overall survival and treatment regimens were based on the phase 3 KEYNOTE-426 and CheckMate214 clinical trials. Survival functions derived from available data were used to project survival beyond trial follow-up.

Cost inputs covered drug acquisition and administration, monthly general treatment including follow-up scans, major adverse event management, best supportive care, and death costs.

RESULTS

: Axi/pembro was estimated to be more effective than ipi/nivo by 0.60 and 0.25 QALYs in the base case and exploratory analysis, respectively. The ICER in the base case was $172,532 per QALY and, in the exploratory analysis, $468,682 per QALY. Sensitivity analyses revealed that our base case model was most sensitive to the prices per milligram of nivolumab, pembrolizumab and axitinib, and axi/pembro was cost-effective only at the upper limit of nivolumab price.

CONCLUSIONS

: Axi/pembro, compared with ipi/nivo, provides additional benefit to aRCC patients regardless of IMDC risk but does not do so cost-effectively. Price reductions would make the cost of axi/pembro commensurate with its clinical value and less financially burdensome to the US healthcare system. Given the poor cost-effectiveness of axi/pembro, expanding the ipi/nivo indication to include favorable risk patients may also be warranted.