A Phase 2 Trial of Intravesical Cabazitaxel, Gemcitabine, and Cisplatin for the Treatment of Non-Muscle-Invasive BCG Unresponsive Urothelial Carcinoma of the Bladder.

Abstract

PURPOSE: A previously reported phase 1 trial at our institution using sequential instillation of intravesical cabazitaxel, gemcitabine, and cisplatin for Bacillus Calmette-Guérin (BCG)-unresponsive non-muscle-invasive bladder cancer (NMIBC) was found to be well-tolerated and safe. Here we present our phase 2 results using this treatment protocol. MATERIALS AND METHODS: In this single-center trial, patients with BCG unresponsive high-risk NMIBC who refused or were ineligible for radical cystectomy received a 6-week intravesical induction course of cabazitaxel and gemcitabine weekly and cisplatin biweekly. Initial clinical response was defined as no evidence of high-grade disease on postinduction cystoscopy with biopsy at 3 months. Responders received maintenance therapy monthly with cabazitaxel and gemcitabine during the first year, and bimonthly for the second year, for a total of 24 months. Flexible cystoscopy was performed every 3 months, and any abnormalities prompted rigid cystoscopy and biopsy. Primary study outcome was recurrence-free survival (RFS) at 12 months. RESULTS: Thirty-three (33) patients were enrolled, of whom 7 were female. The median age was 72 years, and median follow-up was 30.8 months. At enrollment, all patients had high-grade disease and met the criteria for BCG-unresponsive disease. There were no dose-limiting toxicities. RFS at 3 months was 82% (95% CI 69%-95%), decreasing to 73% (95% CI 57%-87%) at 12 months, and 59% (95% CI 42%-76%) at 24 months. Restricted mean survival time (RMST) for RFS at 24 months was estimated to be 18.1 months (95% CI 15-21 months). There were no dose-limiting toxicities. CONCLUSIONS: Combination intravesical cabazitaxel, gemcitabine, and cisplatin is safe and well-tolerated. Recurrence-free survival results are excellent and may represent an improvement from many other available nonsurgical treatments for BCG-unresponsive bladder cancer.