Introduction: Evidence regarding the prognostic impact of immune-related adverse events (irAEs) remains limited in patients with metastatic urothelial carcinoma (mUC) treated with pembrolizumab as a systematic therapy. Thus, we investigated the association between irAE development and oncological outcomes during pembrolizumab therapy.
Methods: We retrospectively evaluated 84 patients with mUC who were treated with pembrolizumab at affiliated institutions and our institution. The associations between irAE development and progression-free survival (PFS), overall survival (OS), and objective response rates (ORRs) were assessed after treatment initiation.
Results: A total of 28 irAEs occurred in 27 patients (32%), with 4 grade = 3 irAEs developed in 4 patients (4.7%). Of 84 patients who treated pembrolizumab, 54 patients (64%) developed disease progression, and 39 patients (46%) died from any cause during follow up period. The PFS and OS were significantly longer in patients with irAEs than that in patients without irAEs (median PFS: 24.1 vs. 5.56 months, p=0.0017; OS: N.R. vs. 12.1 months, p=0.0048 in with irAEs vs. without irAEs) (Figures 1 and 2). Multivariable analysis further revealed that the development of irAEs (hazard ratio: 0.38, P = 0.0058), good Performance Status 1= (P = 0.0379) and single metastatic organ (P = 0.0323) were independent predictors of a longer PFS and development of irAEs (hazard ratio: 0.41, P = 0.0031) was associated with a longer OS. The ORRs were also higher in patients with irAEs (P = 0.0126).
Conclusions: This multi-institutional study showed that presence of irAE was significantly associated with PFS and OS in mUC patients treated with pembrolizumab. Presence of irAEs may be used as a surrogate prognostic marker for PFS and OS in this treatment regimen.
.jpg)
.jpg)
