Phase 2 Trial of Atezolizumab in Bacillus Calmette-Gurin- unresponsive High-risk Non-muscle-invasive Bladder Cancer: SWOG S1605

Background: Although radical cystectomy (RC) is the standard of care for patients with bacillus Calmette-Guerin (BCG)-unresponsive high-risk non-muscle-invasive bladder cancer (NMIBC), many patients are ineligible for surgery or elect bladder preservation. Objective: To evaluate the efficacy and safety of atezolizumab in BCG-unresponsive high-risk NMIBC. Design, setting, and participants: This was a single-arm phase 2 trial in patients with BCG-unresponsive high-risk NMIBC who were ineligible for or declined RC. Intervention: Intravenous atezolizumab every 3 wk for 1 yr. Outcome measurements and statistical analysis: The primary endpoint was the patholog-ical complete response (CR) rate for patients with carcinoma in situ (CIS) determined via mandatory biopsy at 6 mo. Event-free survival (EFS) at 18 mo for patients with non-CIS tumors and treatment-related adverse events (TRAEs) were key secondary endpoints. Results and limitations: Of 172 patients enrolled in the trial, 166 received at least one dose of atezolizumab (safety analysis) and 129 were eligible (efficacy analysis). Of the 74 patients with CIS, 20 (27%) experienced a CR at 6 mo. The median duration of response was 17 mo, and 56% (95% confidence interval [CI] 34-77%) of the responses were durable to at least 12 mo. The 18-mo actuarial EFS rate among 55 patients with Ta/T1 disease was 49% (90% CI 38-60%). Twelve of 129 eligible patients experienced pro-gression to muscle-invasive or metastatic disease. Grade 3-5 TRAEs occurred in 26 patients (16%), including three treatment-related deaths. The study was limited by the small sample size and a high rate of patient ineligibility.