Association of immune-related adverse events (irAEs) with clinical benefit in patients with metastatic urothelial carcinoma (mUC) treated with immune-checkpoint inhibitors (ICIs).

e16038 Background: In other cancers such as metastatic lung and melanoma, pts who experience irAEs may have a greater degree of clinical benefit. We sought to evaluate whether the development of irAEs correlates with clinical benefits in mUC pts. Methods: We identified mUC pts who received PD-1/L1 inhibitors at the Dana-Farber Cancer Institute (DFCI). The severity of irAEs was graded using CTCAE v.5.0. Clinical benefit was defined as any objective reduction (complete- or partial- response) in tumor burden. Fisher’s exact test was used to evaluate for differences in the proportion of pts experiencing clinical benefit between pts experiencing an irAEs within 90 days after starting therapy and those who did not experience an irAEs. The log-rank test assessed differences in progression-free survival (PFS) and overall survival (OS) between cohorts. Results: A total of 199 mUC pts were enrolled between July 2013 and October 2018 [median (range) age, 69.6 (26.6-89.0) years; 141 men (70.9%), 58 women (29.1%)]. 114 (57.3%) pts were treated with anti-PD-1 and 85 (42.7%) with anti-PD-L1. irAEs were observed in 67 pts (33.7%), of which 34 (17.1%) < 90 days from start of therapy. Common irAEs included 20 (29.9%) hypothyroidism, 17 (25.4%) colitis, 12 (17.9%) rash/pruritus, and 10 (14.9%) transaminitis. Grade ≥3 irAEs were observed in 14 pts (20.9%).13 (40.6%) pts with irAE < 90 days experienced clinical benefit compared with 21 (17.8%) of pts with no irAE (p-value = 0.008). No difference (p = 0.26 and 0.18) was observed for either PFS (6-month PFS = 19.2% vs 35.3% for no irAE and irAE < 90 days) or OS (1-year OS = 41.8% vs 57.7% for no irAE vs irAE < 90 days). Conclusions: The development of irAEs within 90 days from starting therapy in mUC pts may herald clinical benefit in pts with mUC. Further evaluation of this potential relationship in a large prospective study is warranted.