OBJECTIVES: Pembrolizumab/axitinib and nivolumab/ipilimumab have shown improvement in overall survival as compared to sunitinib in randomized Phase III trials. Based on these data, both of these regimes were FDA-approved as first-line treatment for advanced renal cell carcinoma (RCC), and have become the standard of care. Given the high price point of immune checkpoint inhibitors, it is important to understand and compare the economic value of these two regimens.

METHODS: From a US societal perspective, a Markov model compared pembrolizumab/axitinib and nivolumab/ipilimumab to sunitinib over a lifetime horizon among treatment-naïve patients with advanced RCC. Under a cohort model design, a single cohort was modeled in each of the 3 treatment arms in parallel, and patients could transition between the health states of progression-free, progression, and death. Patients were allowed to discontinue treatment to second-line therapy or to no therapy. Model inputs were obtained from the KEYNOTE-426 and CheckMate 214 clinical trials, scientific literature, and governmental data sources. Incremental cost-effectiveness ratios (ICERs) were evaluated in terms of cost per quality-adjusted life-year (QALY) gained and sensitivity analyses assessed robustness of model results.

RESULTS: The ICER for pembrolizumab/axitinib versus sunitinib was $850,672 per QALY gained, whereas the ICER for nivolumab/ipilimumab versus sunitinib was $122,480 per QALY gained. One-way sensitivity analyses showed results to be robust to reasonable variation in model inputs, with ICERs most sensitive to drug costs, probability of discontinuing first-line therapy, and disease state-specific health utilities. According to probabilistic sensitivity analyses, pembrolizumab/axitinib and nivolumab/ipilimumab are cost-effective at a willingness-to-pay (WTP) of $150,000 per QALY gained in 2% and 83% of simulations, respectively.

CONCLUSIONS: Based on an accepted WTP of $150,000 per QALY gained, pembrolizumab/axitinib is a low-value therapy compared to sunitinib in patients with advanced RCC. However, at this threshold, nivolumab/ipilimumab represents a cost-effective alternative to sunitinib.