(UroToday.com) The 2023 ASCO annual meeting included a bladder cancer session, featuring a trials in progress presentation by Dr. Guarionex Joel DeCastro discussing a phase 2 trial of intravesical cabazitaxel, gemcitabine, and cisplatin for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder.
In high risk non-muscle invasive bladder cancer (NMIBC) patients, up to 40% will relapse after BCG, with limited salvage multi-agent intravesical therapies available. Based on a preclinical trial in a p53/PTEN genetically engineered mouse model of high grade urothelial carcinoma, multi-drug intravesical therapy with cabazitaxel, gemcitabine, and cisplatin may show benefit:
The goal of this Phase 2 study is to investigate the efficacy of intravesical chemotherapy consisting of sequential cabazitaxel, gemcitabine, and cisplatin in the salvage setting. Phase 1 results reporting on 18 subjects demonstrated adverse events limited to local Grade 1 and 2 toxicities.
This is a Phase 2 trial (NCT02202772) presently enrolling patients with BCG unresponsive NMIBC as defined by the FDA who refuse or are ineligible for radical cystectomy. All patients undergo pre-treatment transurethral resection of bladder tumor and a 6-week regimen of intravesical cisplatin (100 mg), gemcitabine (2 gm), and cabazitaxel (5 mg). Each drug is instilled weekly except for cisplatin, which is given every other week. The treatment protocol for this trial is as follows:
Complete response is defined as having no evidence of cancer on post-induction biopsy (mandatory) and negative urine cytology at 3 months. Complete responders proceed with monthly and bimonthly maintenance therapy without cisplatin in the first and second years, respectively, for a total of 24 months.
To date, 33 patients have been enrolled (meeting the target accrual), of whom seven are female. One patient withdrew consent before first evaluation cystoscopy. The mean age is 72 years, and all patients have previously received at least two prior induction cycles of BCG, and meet FDA criteria for BCG unresponsive disease. All patients have biopsy proven high grade disease at enrollment, with 9 (27.3%) patients having high grade T1 disease, and 21 (63.6%) patients having CIS:
Dr. DeCastro concluded this presentation discussing a phase 2 trial of intravesical cabazitaxel, gemcitabine, and cisplatin for the treatment of non-muscle invasive BCG unresponsive urothelial carcinoma of the bladder by highlighting the following take home messages:
- Salvage options for BCG unresponsive NMIBC are limited
- The sequential cabazitaxel, gemcitabine, and cisplatin protocol has been demonstrated to be safe in a previous phase 1 study, and accrual for this phase 2 is no complete at 33 patients
- The 2-year data is expected within the next 18 months
Presented by: Guarionex Joel DeCastro, MD, Columbia University Irving Medical Center, New York, NY
Written by: Zachary Klaassen, MD, MSc – Urologic Oncologist, Associate Professor of Urology, Georgia Cancer Center, Augusta University/Medical College of Georgia, @zklaassen_md on Twitter during the 2023 American Society of Clinical Oncology (ASCO) Annual Meeting, Chicago, IL, Fri, June 2 – Tues, June 6, 2023.