1974P - 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

Background

Treatment 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.

Methods

This 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

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.

Conclusions

Combination 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 identification

NCT02202772.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Sanofi USA.

Disclosure

All authors have declared no conflicts of interest.