ICI Outcomes Better in PD-L1-Positive Metastatic Urothelial Carcinoma – Renal and Urology News

Programmed death ligand 1 (PD-L1) expression in patients with metastatic urothelial carcinoma (mUC) treated with immune checkpoint inhibitors (ICIs) is associated with improved outcomes, but it is unlikely to be useful as a predictive marker of ICI response, according to investigators.

The findings are from a systematic review and meta-analysis of 14 studies that included 5271 patients with mUC treated with ICIs, of whom 2625 (49.8%) had PD-L1 positive tumors. The objective response rate (ORR) was 13.8% to 78.6% in patients with PD-L1-positive tumors compared with 5.1% to 63.2% in those with PD-L1-negative tumors, Brigida Anna Maiorano, MD, PhD, of IRCCS Casa Sollievo della Sofferenza in San Giovanni Rotondo, Italy, and colleagues reported in JAMA Network Open. The PD-L1-positive group had significant 1.9-fold increased odds of objective response to ICIs compared with the PD-L1-negative group.

Median overall survival (OS) times ranged from 8.4 to 24.1 months in the PD-L1-positive patients compared with 6.0 to 19.1 months in the PD-L1-negative group.

In pooled analyses, the PD-L1-positive group had a significant 29% lower risk for death and 45% lower risk for progression compared with the PD-L1-negative group.

The study results indicate a positive prognostic role of PD-L1 in patients treated with ICIs, a correlation that appears to be independent of the type of ICI, the use of ICIs as single agents or in association with other drugs, and line of treatment. They noted, however, that approximately 1 in 5 PD-L1-negative patients were also responsive to ICIs. The data cannot be ignored, “especially considering response rates and survival that are far longer than with chemotherapeutic agents in second-line or maintenance settings. Therefore, despite the association with prognosis, it seems unlikely to propose PD-L1 as the only marker to guide the use of ICIs in mUC,” the authors wrote.