Anti-PD1/PDL1 Response Tied to Higher Rates of Related Adverse Events in Urothelial Cancer
Patients with metastatic or locally advanced urothelial cancer who responded to anti-PD-1/L1 antibodies were more likely to have related special interest or immune-mediated adverse events than those who didn’t respond to therapy, according to a recent study (J Clin Oncol. 2019 May 22. Epub ahead of print).
Seeking to evaluate the relationship between tumor response rate, overall survival, and related special interest or immune-mediated adverse events (special interest adverse events with topical or systemic corticosteroids) in patients with urothelial cancer who receive anti-PD-1/L1 antibodies, V. Ellen Maher, MD, FDA, Silver Spring, MD, and colleagues conducted an exploratory analysis.
“We examined seven trials in 1,747 patients with metastatic or locally advanced urothelial cancer that led to approval of 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,” they said.
Related and unrelated special interest or immune-mediated adverse events were reviewed, with relationship to study drug determined by the investigator.
A related special interest adverse event was reported in 64% and 34% of patients who did and did not respond to the anti-PD-1/L1 antibody, respectively, whereas a related immune-mediated adverse event occurred in 28% and 12% of patients, respectively.
In addition, a responder analysis demonstrated an increase in overall survival in patients with related special interest adverse events compared with those with no related special interest adverse events (hazard ratio, 0.45; 95% CI, 0.39-0.52).
Approximately 60% of patients who responded to anti-PD-1/L1 antibodies and had related special interest adverse events reported the special interest adverse events before a response was documented.
“Patients who responded to treatment with an anti-PD-1/L1 antibody were more likely to report a related [special interest or immune-mediated adverse events],” Dr Maher and colleagues explained.
“This relationship did not seem to be due to the increased duration of exposure in responding patients. Systemic corticosteroid use did not appear to affect the duration of response,” they concluded.—Hina Khaliq