Atezolizumab is another checkpoint inhibitor with demonstrated activity in metastatic bladder cancer. In the Genitourinary Cancer—Kidney and Bladder Poster Session at the 2020 American Society of Clinical Oncology Virtual Annual Meeting, Peter Black, MD, and colleagues presented the results of the SWOG S1605 trial assessing the efficacy of this agent in patients with BCG-unresponsive high-risk NMIBC.
SWOG S1605 is a single-arm, Phase II registration trial which sought to enroll 135 patients (70 with CIS and 65 with non-CIS histology) with histologically proven BCG-unresponsive high-risk NMIBC who were unfit for or declined radical cystectomy. Enrolled patients received systemic atezolizumab (1200 mg IV) every three weeks for one year. The primary outcome was the pathological complete response (CR) rate at six months as defined by mandatory biopsy. The authors designed the study with a null hypothesis of 30% and an alternative of 50% with a 1-sided alpha = 0.05 and 96% power. The three month CR rate defined by cytology, cystoscopy, and for-cause biopsy, is a key secondary endpoint, in addition to safety.
In the presentation at the 2020 ASCO Virtual Annual Meeting, Dr. Black reported the results of a subset of patients with CIS (with or without concomitant Ta/T1) who received at least one protocol treatment. This represents 75 eligible patients. Of these, two did not receive therapy and were therefore not included in the analytic cohort.
The median age of the included patients was 73 and the median number of BCG doses was 12. In addition to CIS, 14 patients had Ta disease and 16 had T1 disease (30 patients, 41% with non-CIS concomitant histology).
Thirty patients (41.1%, 95% confidence interval [CI] 29.7% to 53.2%) experienced complete response at three months and 19 (26.0%, 95% CI 16.5% to 37.6%) had complete response at six months.
Adverse events were identified in 61 (83.6%) patients. The most frequent of these were fatigue in 36 (49.3%) patients, pruritis in eight (11.0%) patients, hypothyroidism in eight (11.0%) patients, and nausea in eight (11.0%) patients. Serious (Grade 3-5) adverse events (AEs) occurred in nine (12.3%) patients and there was one treatment-related death (myasthenia gravis with respiratory failure and sepsis).
It was concluded that atezolizumab shows similar efficacy to pembrolizumab in this population, meeting the benchmark for initial CR defined by the FDA guidance. Ongoing assessment of the duration of response will be important in guiding the utilization of this approach.
Presented by: Peter C. Black, MD, Urologic Oncologist, Vancouver General Hospital, Research Scientist, Vancouver Prostate Centre, Associate Professor, Department of Urologic Sciences, University of British Columbia, Vancouver, British Columbia
Co-Authors: Catherine Tangen, Parminder Singh, David James McConkey, Scott Lucia, William Thomas Lowrance, Vadim S Koshkin, Kelly Lynn Stratton, Trinity Bivalacqua, Elad Sharon, Wassim Kassouf, Sima P. Porten, Richard Carlton Bangs, Melissa Plets, Seth P. Lerner, Ian Murchie Thompson
Written by: Christopher J.D. Wallis, MD, Ph.D., Urologic Oncology Fellow, Vanderbilt University Medical Center, Nashville, Tennessee, Twitter: @WallisCJD, at the 2020 American Society of Clinical Oncology Virtual Annual Meeting (#ASCO20), May 29th-May 31st, 2020
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