Background: Recent FDA approvals for mRCC treatment have resulted in increased effectiveness, drug choices, and costs. We performed a cost effectiveness analysis (CEA) of six recently approved IO-TKI drug combinations and sunitinib. Methods: We used a Markov simulation model from the healthcare sector perspective with a lifetime time horizon. The 7 treatment drug strategies considered in this model included: (1) atezolizumab + bevacizumab (AB), (2) avelumab + axitinib (AA), (3) pembrolizumab + axitinib (PA), (4) nibolumab + ipilimumab(NI), (5) nibolumab + cabozantinib (NC), (6) lenvatinib + pembrolizumab (LP), and (7) sunitinib (S). Input parameters of drug effectiveness and toxicities to construct the model were based on published randomized studies that led to drug approvals. Direct costs for treatment were derived using the VA Federal Supply Schedule (VAFSS). Markov model simulates patient transition between 3 health states at monthly intervals: progression free, progressive disease, and death. The cost-effectiveness outcome in our model were and life-years (LYs), progression-free life-years (PFLYs) gained, and quality-adjusted life-years (QALYs) with utility values based on published literature. Results: The table highlights results of the CEA. The least expensive drug combination was NI ($442,218) while the most expensive was LP ($963,610). AA yielded the most LYs (5.51) and QALYs (5.62) and LP yielded the most PFLYs (1.64) while NL yielded the least LYs (4.35) and PFLYs (1.47) and LP yielded the least QALYs (4.19). AB and S were absolutely dominated strategies yielding less effectiveness and cost more in terms of effectiveness measures. Depending on acceptable willingness-to-pay (WTP) and effectiveness measures, PA or AA were the most cost-effective strategies. Conclusions: Our analyses suggest that based on direct cost acquisition using VA FSS, PA or AA were cost-effective strategies for mRCC with WTP of $20,000 to $200,000 per QALY.

Note: LY = life-year, PFLY = progression-free life-year, QALY = quality-adjusted life-year, ICER = incremental cost-effectiveness ratio Absolutely dominated strategies were highlighted in grey in each effectiveness measure.