Nivolumab in Patients with Advanced Platinum-Resistant Urothelial Carcinoma: Efficacy, Safety, and Biomarker Analyses with Extended Follow-Up from CheckMate 275 - Expert Commentary

Nivolumab is an FDA-approved immune checkpoint for treating platinum-resistant metastatic or surgically unresectable urothelial carcinoma (mUC). The development of predictive biomarkers to predict response to immune checkpoint inhibitors have been challenging. 



A recent study published by Galsky et al. in Clinical Cancer Research evaluated the long-term outcomes of platinum-resistant mUC patients treated with nivolumab at 3 mg/kg every two weeks in the Phase II CheckMate 275 trial. The investigators assessed the efficacy through the primary endpoint: objective response rate (ORR) and the secondary endpoints: median progression-free survival (PFS) and overall survival (OS).

The ORR was 20.7% (16.1-26.1), median PFS was 1.9 months (1.9-2.3), and median OS was 8.6 months (6.1-11.3, [95% CI]) in all treated patients. TMB positively correlated with ORR (odds ratio [95% confidence interval (CI)]: 2.13 [1.26–3.60], P < 0.05), PFS (hazard ratio [HR] [95% CI]: 0.75 [0.61–0.92], P < 0.05), and OS (HR [95% CI]: 0.73 [0.58– 0.91], P < 0.05). The investigators showed that mutational signature 2 associated with APOBEC correlated with TMB. Patients with PD-L1 expression <1% had a shorter median OS of 6.0 months compared to patients with PD-L1 expression ≥1% who had a median OS of 11.9 months. Interestingly, the combination of TMB and PD-L1 status was a better predictor of OS than PD-L1 alone (P = 0.013). There was no significant interaction between TMB and PD-L1 expression (P = 0.98).

Interestingly, the combination of TMB and PD-L1 status was a better predictor of OS than PD-L1 alone (P = 0.013). There was no significant interaction between TMB and PD-L1 expression (P = 0.98). 

Different tumor types respond differently to immune checkpoint inhibitors. This study highlights the importance of considering TMB, and PDL1 as predictors of response to nivolumab in bladder cancer patients.

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

Reference:

  1. Galsky, Matthew, Abdel Saci, Peter M. Szabo, G. Celine Han, Gary D. Grossfeld, Sandra Collette, Arlene O. Siefker-Radtke, Andrea Necchi, and Padmanee Sharma. "Nivolumab in Patients with Advanced Platinum-Resistant Urothelial Carcinoma: Efficacy, Safety, and Biomarker Analyses with Extended Follow-up from CheckMate 275." Clinical Cancer Research (2020).
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