Comparison of iRECIST with RECIST for capturing treatment response of patients with metastatic urothelial carcinoma treated with pembrolizumab

OBJECTIVE To evaluate the clinical usefulness of Immunotherapy Response Evaluation Criteria in Solid Tumors (iRECIST) in patients with metastatic urothelial carcinoma (UC) treated with pembrolizumab. iRECIST is designed to accurately capture the tumor response treated with immunotherapy. PATIENTS AND METHODS We conducted a multicenter retrospective study evaluating the clinical utility of iRECIST in 91 patients with metastatic UC treated with second-line pembrolizumab. Objective response (OR) and time to progression (TTP) in accordance with both iRECIST and Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 were compared with overall survival (OS) and risk of all-cause mortality and analyzed using log rank and multivariable Cox regression models, respectively. Predictive performance of the criteria was studied using Harrell's concordance index (c-index). The clinical usefulness of each criterion was compared using decision curve analysis. RESULTS Of 57 patients with progressive disease per RECIST, a considerable number of patients were reclassified to immune stable disease (6 [10.5%]), immune partial response (2 [3.5%]), and immune complete response (2 [3.5%]) per iRECIST. Multivariable Cox regression models showed that both OR (hazard ratio [HR]: 0.10, 95% confidence interval [CI]: 0.03-0.35, P = 0.001) and TTP (HR: 0.59, 95% CI: 0.46-0.77, P <0.001) per iRECIST were significantly associated with all-cause mortality. Furthermore, iRECIST had a significant, increased predictability of OS compared with RECIST (OR, c-index: 0.70, increase: 0.04, P = 0.046; TTP, c-index: 0.88, increase: 0.07, P = 0.039). On decision curve analysis, iRECIST presented better net benefit gains than did RECIST. CONCLUSIONS Compared with RECIST, iRECIST could more accurately predict OS of patients with metastatic UC treated with pembrolizumab. iRECIST has a potential to be a new standard for tumor response evaluation of these patients.