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Development of an immune-mediated adverse event (imAE) associated with treatment with a PD-1/PD-L1 inhibitor was associated with improved clinical outcomes among patients with urothelial carcinoma, according to a pooled analysis by the US Food and Drug Administration presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
The study was initiated because it was hypothesized that there may be an association between autoimmune events and outcomes with PD-1/PD-L1 inhibitors because of their immune-modulating mechanisms of action.
Data from 7 trials representing 1747 patients with urothelial carcinoma were examined. Patients who had received prior platinum-based therapy and those who were cisplatin-ineligible were included. The study assessed adverse events of special interest (AESI) considered related to the study drug by each study investigator, focusing on autoimmune events, but could have also included non-autoimmune events such as rash or diarrhea. AESIs that were treated with topical or systemic corticosteroids were termed imAEs.
Treatment-related AESIs occurred in 64% of patients who responded to PD-1/PD-L1 therapy compared with 34% of nonresponders. Similarly, treatment-related imAEs occurred in 28% of responders compared with 12% of nonresponders. This trend persisted after adjustment for duration of treatment exposure for both AESIs (odds ratio [OR], 5.38; 95% CI, 3.06-9.46) and imAEs (OR, 3.77; 95% CI, 2.02-7.03). AESIs occurred both before and after the documented response to the PD-1/PD-L1 inhibitor.
Overall survival (OS) was associated with treatment-related AESIs (hazard ratio [HR], 0.45; 95% CI, 0.39-0.52). Duration of response was not affected by systemic corticosteroid use, which were used for any reason including imAEs (HR, 1.09; 95% CI, 0.70-1.69).
The authors concluded that “there appeared to be a relationship between the development of an autoimmune event and improved patient outcome” with anti-PD-1/PD-L1 treatment of advanced urothelial carcinoma, which was not affected by corticosteroid use.
Maher VE, Fernandes LL, Weinstock C, et al. 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 antibody. Presented at: 2019 American Society of Clinical Oncology (ASCO) Annual Meeting; May 31-June 4, 2019; Chicago, IL. Abstract 4549.