Clinical significance of early kinetics of C‑reactive protein in patients with advanced urothelial carcinoma treated with pembrolizumab: Flare response and baseline levels predict oncological outcomes.

Data on the C-reactive protein (CRP) flare response in patients with metastatic and unresectable urothelial carcinoma (mUC) are limited. The present study aimed to clarify the clinical significance of the CRP flare response in patients with mUC who received pembrolizumab. Between March 2018 and December 2022, patients with mUC who received pembrolizumab following chemotherapy were retrospectively reviewed. Patients were categorized into three groups based on the early kinetics of CRP: i) Flare-responders, in which CRP levels increased >2-fold from baseline (BL) within 1 month after pembrolizumab administration (CRP flare) and decreased to below-BL levels within 3 months; ii) responders, in which CRP levels decreased ≥30% from baseline within 3 months without CRP flare; and iii) non-responders, which included the remaining patients. Tumor response, survival and incidence of immune-related adverse events (AEs) were compared between the groups. Of the 108 eligible patients, 17 (16%), 27 (25%) and 64 (59%) were classified as CRP flare-responders, CRP responders and CRP non-responders, respectively. Objective response rate was higher in CRP flare-responders and CRP responders than in CRP non-responders. Progression-free survival and overall survival were longer in CRP flare-responders and CRP responders than in CRP non-responders. Among CRP flare-responders, patients with low BL CRP levels had a better tumor response and survival than patients with high BL CRP levels. Notably, there was no difference in the incidence of immune-related AEs. In patients with mUC who received pembrolizumab, CRP flare-responders showed favorable oncological outcomes; therefore, BL CRP levels could predict oncological outcomes in CRP flare-responders.