Impact of glucocorticoid treatment and clinical prognostic factors for outcome in patients with advanced urothelial cancer treated with pembrolizumab.

Abstract

Background: Immune checkpoint inhibitors have become a cornerstone in treatment of metastatic urothelial cancer (mUC), but reliable prognostic and treatment predictive factors remain to be defined. Glucocorticoids (GC) are used to manage immune-related adverse events (irAE), and the potential impact on treatment outcome is still unclear.

Objectives: The aim of this study was to explore the impact of GC treatment alongside clinical parameters on outcome in pembrolizumab-treated mUC patients.

Materials and method: A single-center retrospective real-world study was performed including all consecutive mUC patients in first- or second-line treated with pembrolizumab. Multivariate analyses were used to explore the impact of baseline characteristics on response-rate and overall survival (OS). Landmark analysis was applied to adjust for immortal time bias in survival analyzes.

Results: 107 patients were included. Patients developing irAE requiring GC treatment had superior OS compared to those who did not (17.6 months vs. 8.8 months, P = 0.003). Ongoing treatment with GC prior to the initiation of pembrolizumab, ECOG PS >1 and liver metastases were independently associated with worse OS. We constructed a risk-score model where the number of zero, 1, 2 or 3 risk factors correlated to an OS of 11.7 months, 3.8 months, and 3.0 months respectively (P < 0.001).

Conclusion: The development of irAE requiring GC treatment was associated with favorable survial outcomes. Ongoing GC treatment before the commencement of pembrolizumab, ECOG PS >1, and presence of liver metastases were associated with worse OS. We propose a risk-score model to assist clinicians in selecting patients for treatment with pembrolizumab.