OBJECTIVES: We compared the safety of first-line treatments for clear-cell renal cell carcinoma (ccRCC) and second-line immune checkpoint inhibitors (ICIs) versus chemotherapy for platinum-refractory urothelial carcinoma (PRUC). Furthermore, the economic impact of first-line ICI combinations for ccRCC, on the Greek National Health System (ESY), was estimated.

METHODS: CENTRAL, PubMed and clinicaltrials.gov were searched to identify randomized controlled trials (RCTs) with safety outcomes comparing first-line treatments for ccRCC and second-line immunotherapy versus chemotherapy for PRUC. Review Manager software was used for statistical analysis. For the economic analysis, data were collected from the Price Bulletin of Medicines for Human Use, the State Tariff and the Closed Consolidated Hospitals.

RESULTS: Nine RCTs were selected for the systematic review of ccRCC and two for the systematic review of PRUC. The meta-analysis of first-line treatments for ccRCC suggests that ICI combinations have a lower risk of “treatment-related AEs” than sunitinib (Odds Ratio(OR)=0.53, 95% Confidence Interval (CI):0.38-0.73). The meta-analysis of second-line regimens for PRUC suggests that ICIs have a lower risk of “AEs” than chemotherapy (OR=0.32, 95%CI:0.17-0.60). The economic analysis estimated that pembrolizumab+axitinib included an additional cost of 55.154,74€ per patient per year compared with nivolumab+ipilimumab, for first-line treatment of patients with ccRCC, and an additional cost of 64.575,65€ per patient for the median progression-free survival of each treatment for the intermediate- and poor-risk population.

CONCLUSIONS: First-line regimens for ccRCC that include ICIs seem to have a lower risk of AEs than sunitinib. The ICIs, atezolizumab, pembrolizumab, seem to have a lower incidence of toxicity than chemotherapy in patients with PRUC. More studies need to be conducted for safer conclusions, but these inhibitors seem to offer the added benefit of a lower risk of AEs for the patient. ESY expenditure is estimated to be smaller with nivolumab+ipilimumab compared to pembrolizumab+axitinib for patients with ccRCC.