A Clinical Trial of Adjuvant Nivolumab Following Chemoradiation in Localized Muscle-Invasive Urothelial Cancer

Muscle-invasive urothelial cancer (MIUC) has a high recurrence risk following definitive treatment. A recent phase II single-arm trial evaluated nivolumab as adjuvant therapy following chemoradiation in patients with localized or locoregional urothelial carcinoma who were ineligible for or declined radical surgery. Twenty-eight patients received nivolumab 480 mg intravenously every 4 weeks for up to 12 cycles following completion of chemoradiation therapy (CRT). The trial's primary endpoint was 2-year failure-free survival (FFS), with secondary endpoints including recurrence patterns, toxicity, and quality of life. The investigators also analyzed plasma cell-free DNA to correlate genomic features with outcomes.

The study showed a 2-year FFS rate of 33.2% (95% CI 18.5-59.6%). Nine patients (32%) experienced localized progression, and eight (29%) had distant progression. Most patients (89%) had at least one high-risk disease feature, including plasmacytoid differentiation, T4 disease, nodal involvement, multiple tumors, tumors >5 cm, residual disease before CRT, carcinoma in situ, or hydronephrosis. Patients with two or fewer high-risk features demonstrated significantly improved outcomes than those with three or more high-risk features (median FFS of 45.2 months vs. 8.2 months, p=0.0024). Treatment-related adverse events occurred in 18 patients (64.3%), with only three patients (10.7%) experiencing grade 3 events (elevated liver enzymes, diarrhea, and polymyalgia rheumatica). No toxicities higher than grade 3 were observed. Quality of life assessments showed no significant changes during treatment. An exploratory analysis of plasma cell-free DNA revealed that lower copy number instability (CNI) scores before treatment initiation and at cycle 4 correlated with improved overall survival.

This important trial demonstrates that adjuvant Nivolumab following chemoradiation is well-tolerated in patients with localized or locally advanced urothelial carcinoma. This study generates hypotheses regarding important factors for potential patient selection and therapeutic targets in this population, where treatment options remain limited.

Written by: Bishoy M. Faltas, MD, Director of Bladder Cancer Research, Englander Institute for Precision Medicine, Weill Cornell Medicine

References:

Galarza Fortuna GM, Grass D, Maughan BL, et al. Nivolumab adjuvant to chemoradiation in localized muscle-invasive urothelial cancer: primary analysis of a multicenter, single-arm, phase II, investigator-initiated trial (NEXT). J Immunother Cancer 2025;13:e010572. doi:10.1136/jitc-2024-010572.

Read the Abstract

Login