Pd03-02 phase 3 Results of Vicinium in BCG-Unresponsive Non-Muscle Invasive Bladder Cancer

Abstract

INTRODUCTION AND OBJECTIVE:There is an increasing interest in finding a valid alternative for patients with non-muscle invasive bladder cancer (NMIBC). HIVEC-HR is a pilot trial that aims to compare efficacy and safety between BCG and chemohyperthermia (CHT) with mitomycin C (MMC). Here we present our preliminary results once randomization has been completed.METHODS: Open pilot randomized clinical trial 1:1 including patients with high-risk NMIBC according to EAU Guidelines (EudraCT 2016-001186-85). Patients with CIS, intolerance or contraindication for receiving BCG or MMC were excluded. Patients were randomly assigned to one of the following groups:-BCG (TICE strain): 50 mg diluted in 50 mL of sterile saline held for 2 hours in the bladder, one weekly instillation for 6 weeks and maintenance according to SWOG protocol.-CHT: 40 mg MMC diluted in 40 mL of distilled water at 43 C using COMBATÒ recirculation system for 60 minutes, one weekly instillation for 6 weeks and one monthly instillation for 6 months.Follow-up was performed with cytologyþcystoscopy every 3 months as well as upper urinary tract imaging yearly, as stated by EAU Guidelines. Primary endpoint was recurrence-free survival at 24 months. Secondary objectives: safety, progression rate, overall survival and quality of life.RESULTS: Fifty patients randomized (100% recruitment completed), 48 finally starting treatment. Median age is 73 years, 87.6% males and 83% primary tumours. Baseline characteristics were comparable in both groups. Median follow-up is 24.8 months from TURBT. For the BCG group, 6 recurrences (from which 5 progressions to T2) were reported, and only 3 recurrences (from which 2 progressions) happened in the CHT group. Regarding safety profile, adverse events (AE) appeared in 12 patients from CHT and 10 from BCG group, with no differences in the severity (4 patients in each group for CTCAE grade 3). AE in CHT group were mostly grade 1.CONCLUSIONS: According to our trial preliminary results, CHT in high risk NMIBC patients seems at least not to be inferior to BCG in terms of efficacy. Moreover, patients under CHT have milder side effects than those under BCG treatment.

Emerging treatments for bacillus Calmette–Guérin-unresponsive non-muscle-invasive bladder cancer

“…Currently, a phase III VISTA trial ( NCT02449239 ) is underway to confirm the efficacy and tolerability of intravesical vicinium in a larger number of similar BCG-unresponsive NMIBC patients ( Table 4 ). An interim analysis results were presented at the 2020 AUA annual meeting [ 78 ]. In CIS patients (n=89) who recurred within 12 months after the last BCG treatment, intravesical vicinium resulted in CR rates of 40%, 28%, 17%, and 11% at 3, 6, 12, and 24 months, respectively [ 78 ].…”

“…An interim analysis results were presented at the 2020 AUA annual meeting [ 78 ]. In CIS patients (n=89) who recurred within 12 months after the last BCG treatment, intravesical vicinium resulted in CR rates of 40%, 28%, 17%, and 11% at 3, 6, 12, and 24 months, respectively [ 78 ]. More favorable results were observed for papillary-only tumors (n=38), with recurrence-free rates of 71%, 58%, 50%, and 37% at 3, 6, 12, and 24 months, respectively [ 78 ].…”

“…In CIS patients (n=89) who recurred within 12 months after the last BCG treatment, intravesical vicinium resulted in CR rates of 40%, 28%, 17%, and 11% at 3, 6, 12, and 24 months, respectively [ 78 ]. More favorable results were observed for papillary-only tumors (n=38), with recurrence-free rates of 71%, 58%, 50%, and 37% at 3, 6, 12, and 24 months, respectively [ 78 ]. Further, vicinium was well-tolerated with only 52% of patients experiencing treatment-related AEs, the majority being grade 1–2 [ 78 ].…”

“…More favorable results were observed for papillary-only tumors (n=38), with recurrence-free rates of 71%, 58%, 50%, and 37% at 3, 6, 12, and 24 months, respectively [ 78 ]. Further, vicinium was well-tolerated with only 52% of patients experiencing treatment-related AEs, the majority being grade 1–2 [ 78 ]. The favorable toxicity profile of ADC has led to several combination strategies, especially with checkpoint inhibitors.…”

BCG-unresponsive high-grade non-muscle invasive bladder cancer: what does the practicing urologist need to know?

“…Response was defined as negative cytology along with normal cystoscopy or absence of high-grade disease on biopsy. Outcomes have been communicated at the 2020 AUA congress [ 45 ]. As of May 29 th , 2019, the CR rate of the evaluable CIS patients ( n = 89) at 3 months was 40%.…”