Primary Chemoablation of Low-Grade Intermediate-Risk Non-Muscle-Invasive Bladder Cancer Using UGN-102, A Mitomycin-Containing Reverse Thermal Gel (Optima II): A Phase 2b, Open-Label, Single-Arm Trial.

Overview

abstract

PURPOSE: Low-grade intermediate-risk non-muscle-invasive bladder cancer (LG IR NMIBC) is a recurrent disease, thus requiring repeated transurethral resection of bladder tumors (TURBT) under general anesthesia. We evaluated the efficacy and safety of UGN-102, a mitomycin-containing reverse thermal gel, as a primary chemoablative therapeutic alternative to TURBT for patients with LG IR NMIBC. MATERIALS AND METHODS: This prospective, Phase 2b, open-label, single-arm trial recruited patients with biopsy-proven LG IR NMIBC to receive 6 once-weekly instillations of UGN-102. The primary endpoint was complete response (CR) rate, defined as the proportion of patients with negative endoscopic examination, negative cytology, and negative for-cause biopsy 3 months after treatment initiation. Patients with CR were followed quarterly up to 12 months to assess durability of treatment effect. Safety and adverse events were monitored throughout the trial. RESULTS: Sixty-three patients (38 males, 25 females, 33-96 years) enrolled and received ≥1 instillation of UGN-102. Forty-one (65%) achieved CR at 3 months, of whom 39 (95%), 30 (73%), and 25 (61%) remained disease-free at 6, 9, and 12 months after treatment initiation, respectively; 13 patients had documented recurrences. The probability of durable response 9 months after CR (12 months after treatment initiation) was estimated to be 73% by Kaplan-Meier analysis. Common adverse events (incidence ≥10%) included dysuria, urinary frequency, hematuria, micturition urgency, urinary tract infection, and fatigue. CONCLUSIONS: Nonsurgical primary chemoablation of LG IR NMIBC using UGN-102 resulted in significant treatment response with sustained durability. UGN-102 may provide an alternative to repetitive surgery for patients with LG IR NMIBC.