PD-1/PD-L1 inhibitors, commonly used for the treatment of various cancers, have long been associated with immune-mediated adverse events (imAE). Due to the prevalent nature of these events, it has been hypothesised that they may in fact influence clinical outcomes following PD-1/PD-L1 inhibition, especially considering the significant regulatory influence of the immune system. A pooled analysis from the US Food and Drug Administrations has now shown that imAE seems associated with positive clinical outcomes in urothelial cancer patients.
Data derived from 1,747 urothelial cancer patients treated with PD-1/PD-L1 inhibitors across seven trials was analysed, including those who were cisplatin-ineligible, and whom had received prior platinum-based therapy. Adverse events of special interest (AESI), particularly those of an autoimmune nature, were assessed for each patient.
Of the patients studied, 64% presented with treatment-related AESI. These included other, non-immune related events such as diarrhoea or rash. Treatment-related imAE were detected in 28% of responders compared to 12% of non-responders, and this trend remained following adjustment for treatment duration for both AESI and imAE (OR, 5.38; 95% CI, 3.06–9.46, and OR, 3.77;95% CI, 2.02–7.03, respectively). Importantly, overall survival was associated with treatment-related AESI (HR, 0.45; 95% CI, 0.39–0.52), and systemic corticosteroid use, used for the treatment and distinction of imAE compared to AESI, did not appear to regulate the duration of the therapeutic response.
Based off their findings, the authors summarised that, regarding anti-PD-1/PD-L1 treatment, “there appeared to be a relationship between the development of an autoimmune event and improved patient outcome.” This revelation opens up new possibilities for therapeutic intervention, as attenuating these immune-regulating adverse events might additively improve the outcomes from PD-1/PD-L1 treatment, not only for urothelial carcinoma, but potentially other cancer as well.