ASCO 2017: Phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer

Chicago, IL ( At the genitourinary cancer poster session at the 2017 ASCO annual meeting, Dr. Singh and colleagues presented the design of their phase II trial of atezolizumab in BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Certainly, radical cystectomy is the standard of care for patients with BCG-unresponsive high risk non-muscle invasive bladder cancer (NMIBC), however bladder sparing alternatives are needed for those unfit for cystectomy or who refuse surgical treatment. Since there is efficacy of atezolizumab in metastatic urothelial carcinoma1, and the known expression of PD-L1 expression in NMIBC after BCG therapy, the authors hypothesized that atezolizumab may have activity in BCG-unresponsive high risk NMIBC.

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
Twitter: @zklaassen_md

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.