medwireNews: Individuals with urothelial cancer who respond to treatment with PD-1 or PD-L1 inhibitors are more likely to report adverse events (AEs) of special interest, including immune-mediated events, than nonresponders, results of a pooled analysis show.
The exploratory analysis included 1747 patients with locally advanced or metastatic urothelial cancer who had either received prior platinum-based therapy (n=1258) or were cisplatin ineligible (n=489) and were taking part in one of seven clinical trials that ultimately led to approval of a PD-1 or PD-L1 inhibitor in the USA.
As reported in the Journal of Clinical Oncology, treatment-related AEs of special interest occurred in 64% of responding patients and in 34% of patients who did not respond to the PD-1 or PD-L1 inhibitors, while the proportions who experienced a treatment-related immune-mediated AE were 28% and 12%, respectively.
After adjustment for the duration of exposure, the researchers found that responders were a significant 30% more likely than nonresponders to have an AE of special interest and a significant 67% more likely to have an immune-mediated AE.
Furthermore, the relationship between treatment response and either type of AE did not change significantly when the data were analyzed by age, sex, number of prior systemic regimens, and PD-1 versus PD-L1 inhibitor use.
Importantly, 57% percent of responding patients with a treatment-related AE of special interest reported the event before documentation of response, but this did not affect the association between the two variables, V Ellen Maher and colleagues from the US FDA in Silver Spring, Maryland, remark.
Of equal importance according to the investigators was the fact that “[t]he use of systemic corticosteroids did not seem to negatively affect the chances of developing a response and did not seem to affect the duration of response.”
Maher and team also found that, among the responders, both types of AE were associated with improved overall survival. Specifically, patients with treatment-related AEs of special interest had a significant 55% lower risk for death than those without, while the risk was 47% lower among patients with immune-mediated AEs relative to those without.
The investigators caution that interpretation of their findings could be limited by a number of factors, including retrospective nature of the study, a short observational period, and the fact that the proportion of responding patients with a treatment-related AE of special interest or an immune-mediated AE varied among the seven trials.
They add that “[a]dditional work is needed” to determine the significance of the AEs that occurred before response as well other factors, such as AE grade, “that may be predictive of patient outcome.”
By Laura Cowen
medwireNews is an independent medical news service provided by Springer Healthcare. © 2019 Springer Healthcare part of the Springer Nature group
J Clin Oncol 2019; doi:10.1200/JCO.19.00318
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