Background: Immuno-oncology therapies (IOs) and tyrosine kinase inhibitors (TKIs) are recommended for the treatment of aRCC. As new drugs and combination regimens emerge, there is interest in gaining a deeper understanding of optimal treatment sequencing. We aimed to assess clinical and economic outcomes associated with treatment sequences for untreated aRCC patients with IMDC intermediate/poor risk. Methods: A discrete event simulation model was developed to estimate the total costs and survival (in life-years; LYs) over patients’ lifetimes when receiving sequential treatment with nivolumab + ipilimumab (N+I), sunitinib (SUN), pazopanib (PAZ), or cabozantinib (CAB) as first-line (1L) treatment, and nivolumab (NIVO), axitinib (AXI), PAZ, CAB, or lenvatinib + everolimus (LEN+EVE) as second line (2L). Efficacy inputs were derived from the CheckMate 214 trial and a network meta-analysis based on available literature. Safety and cost data were obtained from literature and publicly available sources. Results: N+I initiating sequences were estimated to provide longer survival in mean LYs and lower mean costs/LY versus sequences with 1L TKIs (table). The estimates of incremental cost-effectiveness ratio (ICER) for N+I initiating sequences with 2L TKI monotherapy were well below the willingness-to-pay threshold of $50,000. Using 2L LEN+EVE, compared with 2L monotherapies, provided an incremental survival gain but at costs/LY close to $100,000. Conclusions: Use of 1L N+I followed by TKI monotherapy is estimated to provide longer survival while being more cost-effective versus TKIs followed by IOs or sequences cycling TKIs, mainly driven by a longer time to 2L treatment and longer treatment-free survival with N+I. Clinical trials with head-to-head comparisons of treatment sequences would be necessary to validate the findings of the study.

* Range for the sequences with different 2L options.