Updated Cost-Effectiveness Analysis of Pembrolizumab as an Adjuvant Therapy for Renal Cell Carcinoma After Nephrectomy in the United States

OBJECTIVES: Pembrolizumab was approved by the US Food and Drug Administration as adjuvant treatment of renal cell carcinoma (RCC) at intermediate-high or high risk of recurrence after nephrectomy or after nephrectomy and resection of metastatic lesions, based on prolonged disease-free survival (DFS) versus placebo in the phase 3 KEYNOTE-564 trial. This study aimed to conduct an updated cost-effectiveness analysis of adjuvant pembrolizumab versus routine surveillance alone for RCC post-nephrectomy, incorporating longer-term data from the third interim analysis of KEYNOTE-564 that showed significantly improved overall survival with pembrolizumab.

METHODS: A previously developed Markov cohort model with four states (disease-free, locoregional recurrence, distant metastases, death) was updated to estimate lifetime costs from a US health sector perspective, quality-adjusted life years (QALYs), and life years (LYs). In contrast to the original model, which relied on supplemental data sources to inform post-recurrence transition probabilities, all transition probabilities in the updated model were directly fitted to patient-level KEYNOTE-564 data via parametric multistate modeling. Costs of adjuvant and subsequent treatment, adverse events, disease management, and terminal care were estimated in 2024 US dollars. Utilities were estimated using EQ-5D-5L data from KEYNOTE-564. Deterministic and probabilistic sensitivity analyses were conducted.

RESULTS: Compared to routine surveillance, pembrolizumab increased total costs by $126,631 and provided gains of 1.29 QALYs and 1.45 LYs, with incremental cost-effectiveness ratios of $98,187/QALY and $87,415/LY. The life expectancy gains with pembrolizumab were attributable to longer DFS (1.25 additional LYs in the disease-free state) as well as longer post-recurrence survival (0.20 additional LYs post-recurrence). Internal and external validations supported the modelled survival predictions. At a $150,000/QALY threshold, pembrolizumab was cost-effective in 78.1% of probabilistic simulations.

CONCLUSIONS: When incorporating more mature survival data, pembrolizumab continued to be associated with LY and QALY gains and was found cost-effective relative to routine surveillance as an adjuvant treatment of RCC.