This trial is a phase II, single arm study testing systemic atezolizumab (1200 mg IV) every 3 weeks for one year in BCG-unresponsive high risk NMIBC. The accrual goal is 148 patients, with 135 patients evaluable (10% ineligible, etc), including 70 patients with CIS (with or without concomitant Ta/T1) and 65 with Ta/T1 only. Patients with CIS at baseline will undergo mandatory repeat biopsy at 6 months, and all other patients only for suspected recurrence. The co-primary endpoints are: (i) complete response (CR) at 6 months in the CIS subgroup, and (ii) event-free survival (EFS) at 18 months in the overall population. Secondary endpoints include (i) duration of CR, (ii) progression-free, (iii) cystectomy-free, (iv) bladder cancer-specific, and (v) overall survival in all patients. Treatment will be discontinued for patients with persistent CIS, high grade Ta/T1 recurrence or progression to muscle invasive or metastatic disease. At week 25, patients with no previous on trial biopsies will have a mandatory biopsy, and for those with an on trial negative biopsy will only have a week 25 biopsy for cause. Response will be correlated to expression of PD-L1 and CD8 by immunohistochemistry, and to molecular subtypes and immune signatures by RNA-sequencing.
The study is designed with a significance level of 4.6%, and a power of 96%. If the lower bound of the 90% confidence interval of the 18-month EFS excludes 20%, the investigators will conclude the regimen significantly improves EFS relative to historical data. If ≥28 (40%) of CIS patients respond, atezolizumab will be considered promising. Importantly, successful completion of this trial could lead to a new treatment paradigm for patients with BCG-unresponsive high risk NMIBC who do not desire or are unfit for cystectomy.
Clinical trial: NCT02844816
Presented By: Parminder Singh, Mayo Clinic Arizona, Phoenix, AZ, USA
Co-Authors: Tangen Catherine, Seth P. Lerner, David McConkey, Melissa Plets, M. Scott Lucia, Michael Woods, Trinity Bivalacqua, Wassim Kassouf, Richard Carlton Bangs, Ian Murchie Thompson, Peter C. Black
Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre
at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 – Chicago, Illinois, USA
1. Powles T, Eder JP, Fine GD, et al. MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 2014 Nov 27;515(7528):558-562.