Identification of characteristics associated with long-term survival in patients with metastatic urothelial carcinoma (mUC) who received durvalumab (D) with or without tremelimumab (T) in clinical studies.

Abstract

441 Background: Immune checkpoint inhibitors (ICI) have changed the landscape of mUC, yet outcomes are variable as some patients (pts) do not respond to treatment while others have a durable response. To optimally select pts who may derive benefit from ICIs, predictive factors are required. This retrospective, post-hoc analysis evaluated pt characteristics to determine differences between short and long-term survivors among pts with mUC who received D (anti–PD-L1) with or without T (anti–CTLA-4) in two clinical studies. Methods: Pts with platinum-refractory mUC who received D monotherapy in the phase I/II study 1108 (10 mg/kg Q2W, up to 12 mo) or D+T in the phase I study 10 (D at 20 mg/kg + T at 1 mg/kg Q4W for 4 mo, then D at 10 mg/kg Q2W for 12 mo) were included. Pt characteristics, tumor characteristics, radiological assessments, and biological assessments were collected. The primary outcome measure was long-term overall survival (OS). Pts were categorized as OS ≥2 yrs (from 1st dose of study drug) or OS <2 yrs. A univariate analysis was conducted on each baseline characteristic to assess independent associations with long-term OS; a multivariate logistic regression model was employed including each variable with a p-value ≤0.1 as factors or covariates. Results: A total of 367 pts with mUC were included in the analysis: 88 (24.0%) had OS ≥2 yrs (range: 2.09–4.99) and 279 (76.0%) had OS <2 yrs (range: 0.03–1.98). Pts with OS ≥2 yrs had a significantly higher objective response rates than those with OS <2 yrs (71.6% vs 5.7%; p<0.0001) and a significantly longer duration of response (median 2.3 yrs vs 0.39 yrs; p<0.0001). The characteristics included in the multivariate logistic regression model are listed in the Table. Long-term OS was significantly associated with ECOG PS, PD-L1 status, baseline hemoglobin level, and baseline absolute neutrophils count. Conclusions: Our analyses show that several characteristics, including tumor response to treatment, are associated with long-term OS for pts with mUC treated with D or D+T. Further investigation into these and other characteristics may provide additional insights into long-term survival outcomes with ICIs. [Table: see text]