A phase II trial of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder

BackgroundTreatment options for non-muscle invasive bladder cancer (NMIBC) unresponsive to Bacille Calmette-Guerin (BCG) are limited. A Phase 1 trial at our institution using sequential instillation of intravesical cabazitaxel, gemcitabine, and cisplatin (CGC) in the salvage setting found the regimen to be reasonably well-tolerated and safe. We present our Phase 2 results using this CGC protocol. Funding support was provided by Sanofi.MethodsThis is a single-center, prospective phase 2 trial enrolling patients from June 2020 to March 2023. Patients were diagnosed with BCG unresponsive high-risk NMIBC who refused or were ineligible for radical cystectomy. Patients initially received a 6-week intravesical induction course, which included cabazitaxel (5 mg) and gemcitabine (2000 mg) weekly and cisplatin (100 mg) biweekly. Determination of initial response at 3 months was based on post-induction cystoscopy with mandatory biopsy. Responders received maintenance monthly and bimonthly therapy in the first and second years, respectively, for a total of 24 months. Flexible cystoscopy and urine cytology were completed every three months, and any abnormalities prompted rigid cystoscopy.Results Table: 1974P Actual recurrence and cystectomy free survival Time (mos) # Recurred Recurrence Free Survival Cystectomy Free Survival 3 6 82% 100% 6 8 76% 100% 9 9 73% 97% 12 9 73% 97% 15 9 73% 97% Thirty-three (33) patients were enrolled, of whom seven were female. Mean age was 72 years, and median follow-up was 20 months (range 16.7 - 42.5). Tumor pathology of subjects at study entry were as follows: TaHG - 18%; T1HG - 33%; CIS only - 48%; Ta/T1HG + CIS - 21%. There were no related adverse events Grade 3 or greater. At 3 months 82% of patients had no evidence of recurrence. Recurrence free and cystectomy free survival at 15 months were 73% and 97%, respectively.ConclusionsCombination intravesical CGC appears to be a highly effective and well-tolerated treatment option for BCG unresponsive patients. The majority of those in our study experienced a durable response without need for radical cystectomy during the study period.Clinical trial identificationNCT02202772.Legal entity responsible for the studyThe authors.FundingSanofi USA.DisclosureAll authors have declared no conflicts of interest.