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.

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.