Adding mitomycin (MM) to bacillus Calmette-Guérin (BCG) as adjuvant intravesical therapy for high-risk, non–muscle-invasive urothelial bladder cancer (NMIBC): BCGMM; ANZUP 1301.

Abstract

TPS4617 Background: Adjuvant intravesical BCG decreases disease recurrence and progression in high-risk, NMIBC, however recurrence occurs in 30% of those affected, despite optimal therapy. Meta-analyses evaluating addition of intravesical MM to BCG showed lower rates of recurrence and cancer-specific mortality in people with NMIBC who received combination regimens. Phase 3 randomized trials to definitively test this combination are lacking. The BCGMM trial (NCT02948543) will determine the effects of adding MM to the standard BCG after resection of high-risk NMBIC. This is the largest study evaluating this approach in high-risk NMIBC, is of particular relevance given the current BCG shortage, and has the potential to change global practice. Methods: This open-label phase 3 trial is randomizing 500 participants stratified by stage, site of disease, and presence of carcinoma in-situ, in a 1:1 ratio to Arm A (BCG induction weekly x6 then monthly x10) or Arm B (BCG weeks 1, 2, 4, 5, 7, 8; months 4, 5, 7, 8 + MM weeks 3, 6, 9; months 3, 6, 9, see figure below). This provides 85% power to detect an absolute improvement of 10% in 2-year disease free survival (DFS) at 2p = 0.05. Stage 1 (n = 130) was to determine rates of treatment completion, activity reflected by cystoscopic findings at 3 months, adverse events, resource use, and health related quality of life, established feasibility. Stage 2, including an additional 370 participants, will provide information on DFS, time to recurrence and progression, overall survival, and identification of potential predictive biomarkers, is estimated to complete accrual by Q2 2023. Progress As of Jan 2023, 484 of 500 planned participants have been recruited from 16 Australian and 1 UK site. In stage 1, successful treatment completion, defined as 75% or more of planned treatment doses, was achieved by 76% in the experimental group (BCGMM) versus 60% in the control group (BCG alone). Clinical trial information: NCT02948543 .