Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION)

Abstract

Purpose: We evaluate the efficacy and safety of UGN-102 chemoablation for the primary treatment of patients with recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer.

Materials and methods: ENVISION is an ongoing, multinational, single-arm, phase 3 study in patients with a biopsy-proven recurrence of untreated low-grade intermediate-risk nonmuscle-invasive bladder cancer. Patients received 6 weekly intravesical instillations of UGN-102 (mitomycin; outpatient setting) and were evaluated at 3 months. Patients achieving complete response (CR; negative cystoscopic examination, cytology, and for-cause biopsy) were surveilled regularly until recurrence, progression, or death. Patients who remain disease-free will be followed up to 5 years, and further results will be reported in the future.

Results: Of 240 patients enrolled, 228 (95%) received all 6 planned doses; 191 (80%; 95% CI, 73.9-84.5) achieved CR at 3 months, with an 82% (95% CI, 75.9-87.1) probability of response 12 months later. Median duration of response was not estimable over a median 13.9-month follow-up period. The most common adverse events (≥5.0% of patients) were dysuria, hematuria, UTI, pollakiuria, fatigue, and urinary retention; generally mild/moderate and resolved/resolving. Serious adverse events were observed in 29/240 (12.1%); 2 were treatment related (urinary retention/urethral stenosis), and both resolved.

Conclusions: Primary chemoablation with UGN-102 in patients with recurrent low-grade intermediate-risk nonmuscle-invasive bladder cancer resulted in an 80% CR rate. Patients achieving a CR had an 82% likelihood of remaining disease-free 1 year later. The benefit-risk profile was favorable, supporting UGN-102 as a nonsurgical alternative for transurethral resection of bladder tumors in this patient population. Limitations of this study included lack of tumor sizing after the diagnostic biopsy.

Trial registration: ClinicalTrials.gov Identifier: NCT05243550.

Keywords: ENVISION; LG-IR-NMIBC; chemoablation; recurrent bladder cancer.

Figure 1.

Patient flow diagram. Intention-to-treat (ITT)/safety analysis set comprises all patients who have been enrolled in the trial and who have received any instillation of UGN-102. Three-month imputed complete response analysis set comprises all patients from the ITT analysis set who had either observed or imputed complete response at the 3-month disease assessment. AE indicates adverse event.

Figure 2.

Kaplan-Meier plot of duration of response in patients with a complete response (CR) at 3 months. Events include recurrence, progression, or death.

Figure 3.

Swimmer plot of duration of response in patients with a complete response at 3 months. Events include recurrence, progression, or death.