Bladder cancer is a common disease in the elderly population. Approximately 570,000 cases are diagnosed annually worldwide, with a median age at diagnosis of 70 years. Muscle-invasive bladder cancer (MIBC) comprises about 25% of bladder cancer diagnoses, and many patients with MIBC may not receive curative-intent therapy. Elderly patients are the most affected by this unmet need.
TAR-200 is a novel treatment consisting of a small, flexible, silicone delivery system that provides sustained, local release of gemcitabine to the bladder over a 21-day dosing cycle. Results of the global, phase 1 TAR-200-103 study, which evaluated the safety, tolerability, and efficacy of TAR-200 in patients with MIBC who refused or were unfit for curative-intent therapy, were presented at the American Urological Association 2023 Annual Meeting.
Patients eligible for the study had cT2-cT3bN0M0 urothelial carcinoma of the bladder. A total of 35 patients were enrolled, and 68.6% of patients were male. The median age was 84 years old. Patients received up to 4 consecutive 21-day cycles of TAR-200 during an 84-day induction period within 7 weeks of transurethral resection of bladder tumor.
Patients were eligible for 3 optional additional quarterly maintenance cycles beginning on day 180, and a final safety follow-up visit occurred after the maintenance period (30 days after last TAR-200 removal). Patients were then given the option to enter a 24-month surveillance period to monitor for recurrence and overall survival (OS).
The primary end points of the study were safety and tolerability at 84 days. Secondary end points included rates of clinical complete response and partial response measured by cystoscopy, biopsy, and imaging; duration of response; and OS. Treatment-related adverse events occurred in 15 of the 35 patients, and 2 patients experienced treatment-related adverse events that led to the removal of TAR-200.
At 3 months, complete response and partial response rates occurred in 11 patients (31.4%) and 3 patients (8.6%), respectively, yielding an overall response rate of 40.0% (14/35; 95% CI, 23.9-57.9). Median overall survival and duration of response were 27.3 months (95% CI, 10.1-not estimable) and 14 months (95% CI, 10.6-22.7), respectively. The progression-free rate at 12 months was 70.5%.
TAR-200 demonstrated beneficial preliminary efficacy as well as safety and tolerability in the study’s elderly and frail cohort and in those with limited treatment options.