Impact of IRAES on the outcomes of pembrolizumab therapy in patients with MUC: A comprehensive analysis of severity and the type and number of affected organs

Abstract

Background

Immune-related adverse events (irAEs) are reportedly associated with favorable outcomes in patients with metastatic urothelial carcinoma (mUC) receiving pembrolizumab. Previous studies on this topic focused on the severity of irAEs. The type and number of organs affected by irAEs may also be associated with the therapeutic outcomes.

Methods

The present, retrospective study included 146 patients with mUC receiving pembrolizumab between January 2018 and March 2022. The primary endpoints were the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) associated with the type and number of organs affected by irAEs and the severity of the symptoms. IrAEs were graded using the Common Terminology Criteria for Adverse Events version 5.0. The treatment response was assessed using the Response Evaluation Criteria in Solid Tumors version 1.1. Cox proportional hazards was used to assess for any association between the variables and survival. Time-dependent analysis was used to assess the status of irAEs as a prognostic factor.

Results

IrAEs ≥ grade (G) 2 were observed in 48 (33%) patients, of whom 9 (6%) had multiple irAEs. IrAEs ≥G2 were significantly associated with a higher ORR (57% vs. 22% for <G2; P < 0.001) and longer PFS and OS (both P < 0.001). Multiple irAEs ≥G2 had a higher ORR (89% vs. 49% for a solitary irAE ≥ G2 vs. 22% for irAEs < G2; P < 0.001) and a significantly longer PFS and OS (both P < 0.001). Skin, lung, and liver-related irAEs ≥G2 were significantly associated with a higher ORR and a longer PFS and/or OS. On multivariable analysis, the severity of irAEs ≥G2 vs. <G2 and the number of irAEs ≥G2 were independently and significantly associated with longer OS (P = 0.04), PFS, and OS (both P < 0.001). Skin irAEs ≥G2 were independently associated with longer PFS and OS (both P = 0.07).

Conclusions

The severity and number of irAEs and the organs affected by them appeared to be relevant to the therapeutic efficacy of pembrolizumab in patients with mUC.