An FDA analysis of the association between adverse events and outcome in patients with urothelial cancer receiving a programmed death protein 1 or programmed death ligand 1 (anti-PD-1/L1) antibody.

Abstract

4549 Background: To assess the relationship between tumor response rate, overall survival, and the development of related adverse events of special interest (AESIs) or related immune-mediated adverse events (imAEs) in patients with urothelial cancer treated with anti-PD-1/L1 antibodies. Methods: We examined seven trials that led to drug approval and which included 1747 patients with metastatic or locally advanced urothelial cancer treated with an anti-PD-1/L1 antibody. Five trials enrolled patients who had received prior platinum-based therapy and two enrolled patients who were cisplatin-ineligible. The datasets were searched for AESIs, related AESIs, imAEs, and related imAEs. The relationship to study drug was determined by the Investigator. Immune-mediated adverse events were defined as AESIs treated with topical or systemic corticosteroids. Results: In these exploratory analyses, a related AESI was reported in 64% of responding patients and in 34% of patients who did not respond to the anti-PD-1/L1 antibody while a related imAE occurred in 28% and 12% of patients who did and did not respond to study drug, respectively. In a responder analysis, an increase in overall survival was seen in patients with related AESIs compared to those with no related AESI [hazard ratio (HR) 0.42; 95% CI: 0.37, 0.49]. Fifty-seven percent of responding patients with a related AESI reported a related AESI prior to documentation of response. Conclusions: Patients who responded to treatment with an anti-PD-1/L1 antibody were more likely to report a related AESI or related imAE. This relationship did not appear to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response.