Impact of tumor burden or focality in recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer on response to treatment with UGN-102: A substudy of the phase 3 ENVISION trial.
Authors: Prasad Sandip M , Shishkov Dimitar , Mihaylov Nikola V , Khuskivadze Alexandre , Genov Pencho , Terzi Vasyl , Kates Max , Huang William C. , Louie Michael J , Raju Sunil , Burger Brent , Meads Andrew , Schoenberg Mark ,   ENVISION Study Group
Published: February 2025

776

Background:
The ENVISION phase 3 study (NCT05243550) treated patients withlow-grade intermediate-risk non-muscle-invasive bladder cancer (LG-IR-NMIBC) with UGN-102, a reverse thermal hydrogel containing mitomycin. Primary efficacy and safety results were previously reported. Complete response (CR) rate at 3 months was 79.6%, with an 82.3% probability of remaining in response 12 months later by Kaplan-Meier estimate. We conducted a post-hoc analysis to evaluate if certain tumor characteristics influenced response rate and durability.
Methods:
In the single-arm ENVISION study, 240 patients with LG-IR-NMIBC received 6 weekly intravesical instillations of UGN-102; 3 months after the first dose, patients were examined for the presence of bladder cancer using cystoscopy, urine cytology testing, and for-cause biopsy. Patients achieving CR (no detectable disease) entered the follow-up period and were surveilled regularly for recurrence. Between group comparisons were performed for CR rate (CRR) at 3 months and duration of response (DOR) 12 months after achieving CR in patients with tumor burden ≤ or >3 cm (calculated as total length of all tumors), and for single vs multiple tumors. Hazard ratios (HRs) of DOR were calculated using a Cox Proportional Hazards (PH) model, and p-values calculated using a log-rank test; p-values for the comparison of CRR were calculated using Fisher’s Exact Test.
Results:
CRR at 3 months was 82.8% vs 73.2% for patients with tumor burden ≤3 cm and >3 cm, respectively. Of the patients with CR at 3 months, 15.4% vs 20% experienced recurrence of LG disease, progression (either in stage or grade), or death by 15 months. In patients with multiple vs single tumors, 3-month CR was 79.3% vs 82.9%, with recurrence rates of 18.5% vs 11.8%. DOR HRs were not statistically significant for any comparison made (table).
Conclusions:
Although a non-significant higher event rate was observed at 3 months for patients with a higher tumor burden, the CRR was robust, and the majority of patients remained event free at 15 months. These results demonstrate that chemoablation using UGN-102 results in a high, clinically meaningful CRR in patients with recurrent LG-IR-NMIBC, regardless of tumor burden or multifocality. Study limitations were the small sample size of the comparator groups, single arm design, and post-hoc nature of the analysis. UGN-102 may represent a valuable treatment option for many patients with LG-IR-NMIBC. Clinical trial information:
NCT05243550
.

CR at 3 months
CRR(95% CI) / p value*
Recurrence within 15 months
DOR HR(95% CI) / p value*

Tumor size

≤3 cm>3cm
149/180 (82.8%)30/41 (73.2%)
1.13 (0.93–1.38) / p=0.1854
23/149 (15.4%)6/30 (20.0%)
0.777 (0.317–1.909) / p=0.5816

Tumor count

MultipleSingle
157 /198 (79.3%)34/41 (82.9%)
0.96 (0.82 –1.12) / p=0.6740
29/157 (18.5%)4/34 (11.8%)
1.644 (0.578–4.677) / p=0.3459

*Nominal.