Atezolizumab (atezo) and subsequent therapies in patients (Pts) with metastatic urothelial carcinoma (mUC) outside clinical trials.

Abstract

432 Background: The use of immune checkpoint inhibitors (ICI) has revolutionized treatment of mUC. Little is known about the outcomes and safety profile of pts treated with ICI outside of clinical trials, as well as about responses to subsequent therapies. Methods: A retrospective analysis of consecutive mUC pts who received ≥1 dose of atezo 1200 mg every 3 weeks from May 2016 through April 2017 was conducted. Exploratory assessments included overall response rate according to RECIST v1.1, progression-free survival (PFS) and overall survival (OS) since time of treatment initiation, and treatment-related adverse events (TRAE) according to CTCAE v4.03. Results: A total of 79 pts were identified; median age 72 (29-93), 71% men, 27% never smokers, 66% pure urothelial histology, 49% visceral disease, 76% ECOG PS 0-1 and 61% with 1-2 Bellmunt risk factors. Most pts (79%) had primary tumor in bladder, 62% prior surgery and 75% ≥ 1 prior treatment. Most pts (71%) had 1-2 prior lines of treatment, 4% of pts had 3 lines, and 25% of pts had no prior systemic treatment. Pts received a median of 4 atezo doses (1-18) and median treatment duration was 3.2 months (95%CI 1.9-4.5). In 55 pts evaluable for response, 25% had partial response, 36% stable disease and 38% progressive disease, with a median time to best response of 2.7 months (1.3-7.4) and median PFS 4.5 months (95%CI 3.4-5.6). Estimated OS for the entire cohort was 8.3 months (median not reached) and was not significantly different based on prior therapy. TRAE of any grade were noted in 89% of pts and mostly included fatigue (63%) and anorexia (28%). Two pts had grade 4 hyperbilirubinemia, and no toxic deaths were noted. At time of data analysis, 34% of pts remained on atezo, 16% received 1-2 subsequent treatments with median duration of 1.3 months ( 95%CI 0.5-2.2) and 8% PR as best response, 41% were referred to hospice or died, and 9% were lost to follow-up. Conclusions: Pts with mUC treated with atezo had comparable outcomes and toxicity to those reported in clinical trials. Pts who progressed on atezo were unlikely to receive subsequent treatment and the benefit of such treatment was limited. Results may impact clinical trial designs and timing in regard to ICI.