Tivozanib versus Sorafenib as Subsequent-Line Therapy for Advanced Renal Cell Carcinoma: A Cost-Effectiveness...

The incidence of advanced renal cell carcinoma (aRCC) continues to rise in the United States. While first-line combinations of immune checkpoint inhibitors and tyrosine kinase inhibitors have improved outcomes, most patients eventually require subsequent-line therapy. The Phase III TIVO-3 trial demonstrated that tivozanib significantly prolongs progression-free survival (PFS) compared to sorafenib in relapsed or refractory aRCC, though without overall survival advantage. However, its economic value remains unestablished. This study aimed to evaluate the cost-effectiveness of tivozanib versus sorafenib from a US healthcare perspective.

A Partitioned Survival Model was developed using TreeAge Pro 2022 to simulate clinical outcomes over a 10-year lifetime horizon. Survival data were reconstructed from TIVO-3 trial Kaplan-Meier curves and extrapolated using standard parametric distributions. The model incorporated direct medical costs, including drug acquisition, monitoring, adverse event management, and terminal care. Health utilities were sourced from published literature. Costs and quality-adjusted life years (QALYs) were discounted at 3% annually. Sensitivity and scenario analyses were performed to assess model robustness.

In the base-case analysis, tivozanib yielded 1.65 QALYs at a cost of $634,441.98, compared to 1.61 QALYs and $438,239.46 for sorafenib, corresponding to an incremental QALY gain of 0.04. The incremental cost-effectiveness ratio (ICER) was $4,865,127.00 per QALY, substantially exceeding the $150,000 per QALY threshold. Probabilistic sensitivity analysis indicated that tivozanib was unlikely to be cost-effective at current pricing. Scenario analysis revealed that tivozanib only achieves cost-effectiveness if its acquisition cost is reduced by more than 49%.

Despite superior PFS, tivozanib is unlikely to be a cost-effective subsequent-line therapy for aRCC compared to sorafenib at its current US market price. The high ICER is primarily driven by substantial drug costs relative to modest incremental health gains. Substantial price reductions are necessary to improve its value proposition within the US healthcare system.