37 Cost-effectiveness of treatment sequences with front-line nivolumab+ipilimumab therapy vs immuno-oncology+tyrosine kinase inhibitor therapies in intermediate/poor-risk metastatic renal cell carcinoma
Authors: Ebrahimi Hedyeh , Berardi Andrea , Smare Caitlin , Pavlidou Eleni , Guttenplan Sarah B , Eiffert Sam , Rosenblatt Lisa , Kurt Murat , Yin Xin , Chehrazi-Raffle Alexander 
Published: August 2024

Abstract

Background
Immuno-oncology (IO) and vascular endothelial growth factor (VEGF) targeted tyrosine kinase inhibitor (TKI) combinations have transformed the treatment of metastatic renal cell carcinoma (mRCC). However, there is a lack of evidence regarding the most cost-effective sequencing of these systemic therapies. This study aimed to assess the expected health and economic outcomes of various treatment sequences for newly diagnosed patients with intermediate/poor-risk RCC from a US payer perspective.

Methods
We developed a model using a continuous time micro-simulation framework. First-line treatment options included: nivolumab+ipilimumab, nivolumab+cabozantinib, pembrolizumab+lenvatinib, and pembrolizumab+axitinib. Second-line treatment options included: cabozantinib and everolimus+lenvatinib. In both lines, the source data for the overall survival (OS) and progression-free survival (PFS) distributions were obtained from the registrational randomized controlled trials (RCTs) of each therapy. The analysis included costs associated with drug acquisition in the US wholesale setting, drug administration and monitoring, management of treatment-related adverse events, disease management, and terminal care. Treatment duration for all first-line IO and TKI therapies was capped at 2 years. Quality-adjusted life-years (QALYs) were estimated by multiplying time in each phase of the disease by phase-specific utility values estimated from the CheckMate 214 trial data using US tariffs. The analysis was run 1000 times for cohorts of 100 patients over a 20-year time horizon. All costs and health outcomes were discounted annually at a 3% rate.

Results
Average per-patient QALYs were estimated for each sequence of interest: nivolumab+ipilimumab followed by cabozantinib (3.59), nivolumab+ipilimumab followed by lenvatinib+everolimus (3.26), pembrolizumab+axitinib followed by cabozantinib (3.14), pembrolizumab+axitinib followed by lenvatinib+everolimus (2.97), pembrolizumab+lenvatinib followed by cabozantinib (3.51), and nivolumab+cabozantinib followed by lenvatinib+everolimus (2.99). Average per-patient costs were estimated for each sequence of interest: nivolumab+ipilimumab followed by cabozantinib ($468,856), nivolumab+ipilimumab followed by lenvatinib+everolimus ($491,259), pembrolizumab+axitinib followed by cabozantinib ($675,714), pembrolizumab+axitinib followed by lenvatinib+everolimus ($700,411), pembrolizumab+lenvatinib followed by cabozantinib ($837,888), nivolumab+cabozantinib followed by lenvatinib+everolimus ($873,377). First-line drug acquisition costs accounted for the majority of costs for all sequences.

Conclusions
Based upon our model using data from registrational RCTs, first-line nivolumab+ipilimumab followed by cabozantinib represents the dominant treatment strategy for intermediate/poor-risk mRCC patients in the US, offering estimated cost savings of up to 45% when compared to IO+TKI options. Additional studies are needed to elucidate whether these cost savings translate to the real-world setting.