Atezolizumab (atezo) in platinum (plat)-treated locally advanced/metastatic urothelial carcinoma (mUC): Updated OS, safety and biomarkers from the Ph II IMvigor210 study

Abstract

Background: Plat-refractory mUC pts have no therapies that significantly extend OS, which is < 7 mo in the 2L setting (Bellmunt J Clin Oncol 2009). Atezo (anti-PDL1) has demonstrated tolerability and efficacy in plat-treated mUC. Here we present updated data on pts with ≈ 1.5-y median follow-up (mFU). Methods: Pts who had progressed during/following plat received 1200 mg atezo IV q3w and could continue treatment past RECIST v1.1 PD until loss of clinical benefit. Co-primary endpoints were confirmed RECIST v1.1 ORR (central review) and immune-modified RECIST ORR (per investigator). PD-L1 status on immune cells (IC) was scored centrally (SP142 IHC assay): IC2/3, 1, 0. Results: 310 pts (median 66 y) were evaluable: 78% had visceral mets; 43% had ≥ 2 prior mUC regimens. RECIST v1.1 ORR was 28% in IC2/3 pts (95% CI: 19, 38), 19% (14, 25) in IC1/2/3 and 16% (12, 20) in all pts. Both CRs (15% in IC2/3; 9% in IC1/2/3; 7% in all pts) and PRs occurred in pts with poor prognostic factors and were durable (71% ongoing at the 14 Mar 2016 data cut off ). mDOR was not reached with a 17.5-mo mFU (range, 0.2 + -21.1). Among 134 pts continuing treatment post PD, 19% had subsequent ≥ 30% decrease in target lesions. 1-y OS was 50% in IC2/3 pts (95% CI: 40, 60), 40% (33, 47) in IC1/2/3 and 37% (31, 42) overall, with 30% of all pts alive. Overall and subgroup mOS are in the Table. Atezo remained well tolerated with low rates of immune-mediated AEs and discontinuations. 70% of pts had a related AE (mostly fatigue [31%]; nausea [14%]), 16% were G3-4 (no G5 events). > 1-y safety, biomarker correlates of OS (immune gene expression, mutation load) and TCGA classification will be presented. Conclusions: Heavily pre-treated mUC pts on atezo monotherapy had durable responses, with encouraging OS. Combined with favorable safety, atezo may transform treatment of plat-treated mUC. A randomized Ph III study vs chemo in this population is ongoing (NCT02302807). (Table Presented).