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.

Abstract

4597 Background: In the ENVISION pivotal phase 3 study (NCT05243550) patients with low-grade intermediate-risk non-muscle invasive bladder cancer (LG-IR-NMIBC) were treated with UGN-102, a reverse thermal hydrogel containing mitomycin. Primary efficacy and safety results were previously reported. Complete response rate (CRR) at 3 months was 79.6%, with an 82.3% probability of remaining in response at 12 months by Kaplan–Meier estimate. Here, we present a post-hoc analysis evaluating if multifocality and tumor size 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 complete response (CR; no detectable disease) underwent follow-up with surveillance cystoscopy. In pre-specified subgroups, comparisons of patients with tumor burden (calculated as total length of all tumors) ≤3cm vs > 3 cm and single vs multiple tumors were performed for CRR at 3 months and hazard ratios (HRs) of duration of response (DoR) at 12 months after achieving CR. For the comparison of CRR, p values were calculated using Fisher’s Exact Test. HRs of DoR were calculated using a Cox proportional hazards model, and p values calculated using a log-rank test. Comparisons were not powered to identify a difference and p values were unadjusted for multiple comparisons. Results: CRR at 3 months was 82.8% vs 73.2% for patients with tumor burden ≤3 cm and > 3 cm, respectively. Of patients with CR at 3 months with tumor burden ≤3 cm and > 3 cm, 15.4% vs 20%, respectively, experienced either recurrence of LG disease, progression (either stage or grade), or death by 15 months. In patients with multiple vs single tumors, 3-month CR was 79.3% vs 82.9%; recurrence rates were 18.5% vs 11.8%. DoR HRs were not statistically significant for any comparison made (Table). Conclusions: The CRR and DoR were favorable in all subgroups and no significant differences were observed. Study limitations were the small sample size of 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 ratio(95% CI)/p value Recurrence within 15 months a DoR HR (95% CI)/p value Tumor burden≤3 cm>3 cm 149/180 (82.8%)30/41 (73.2%) 1.13 (0.93, 1.38)p=0.1854 b 23/149 (15.4%)6/30 (20.0%) 0.777 (0.317, 1.909)p=0.5816 b Tumor countMultipleSingle 157/198 (79.3%)34/41 (82.9%) 0.96 (0.82, 1.12)p=0.6740 b 29/157 (18.5%)4/34 (11.8%) 1.644 (0.578, 4.677)p=0.3459 b a 3-month CR patients only. b Nominal. CI, confidence interval.