OBJECTIVES: Three tyrosine kinase inhibitor + immuno-oncology (TKI+IO) regimens (i.e., cabozantinib+nivolumab [C+N], axitinib+pembrolizumab [A+P], and lenvatinib+pembrolizumab [L+P]) have been approved by the Food and Drug Administration (FDA) for the first-line treatment of advanced renal cell carcinoma (aRCC). Given the limited information on costs of treating adverse events (AEs), we estimated the costs of all-cause grade 3/4 AEs for C+N, A+P, and L+P from the CheckMate 9ER, KEYNOTE-426, and CLEAR trials, respectively.

METHODS: All-cause grade 3/4 AEs that occurred in ≥5% of patients treated with C+N, according to the FDA product prescribing information, were evaluated including: increased alanine aminotransferase (ALT), increased aspartate aminotransferase, increased lipase, diarrhea, fatigue, palmer-plantar erythrodysesthesia, and hypertension. AE unit costs were derived from 2018 Healthcare Cost and Utilization Project inpatient data (principal diagnosis based on Clinical Classifications Software-Refined codes) and inflated to 2021 USD. Total costs are the sum-product of AE probabilities and corresponding unit costs. Median duration of follow-up, total AE costs, and the highest AE cost driver are reported for each treatment regimen.

RESULTS: Median duration of follow-up was longest among patients receiving L+P, followed by C+N and A+P, with 26.6, 18.1, and 12.8 months, respectively. Patients treated with C+N incurred the lowest total AE-related costs ($7,755), followed by patients treated with A+P ($8,757) and L+P ($11,220). The AE resulting in the highest cost among patients treated with C+N and L+P was increased lipase ($1,622 and $3,940, respectively) and increased ALT for patients treated with A+P ($2,318).

CONCLUSIONS: US patients with aRCC treated with C+N experienced the lowest total AE-related costs, followed by A+P and L+P. The top AE cost driver was increased lipase for two of the regimens under study. Our study suggests that AE costs vary among TKI+IO regimens and could be important in assessing cost-effectiveness and budget impacts.