ANZUP 1301 was a randomised trial designed to determine whether adding mitomycin to BCG (BCG+MM) could improve oncologic outcomes in high-risk NMIBC. Although superiority was not established, ANZUP 1301 demonstrated BCG+MM had similar efficacy to BCG alone, with important advantages in treatment completion, BCG sparing, and signals of potential benefit in higher-risk patients.
Efficacy outcomes in context
In the primary analysis, BCG+MM achieved comparable oncologic efficacy (disease-free survival, DFS) to BCG monotherapy, with no signal of inferiority. All key efficacy endpoints favoured the combination arm, but the differences were within the play of chance, so superiority was not established. These findings are reassuring, indicating that modifying standard BCG therapy through the addition of mitomycin did not compromise cancer control.
This is a critical point. Any alternative to BCG monotherapy must, at a minimum, preserve its established oncologic effectiveness. Results from ANZUP 1301 support this hypothesis, and provide a coherent argument for considering additional clinical advantages beyond efficacy alone.
Safety and toxicity
A common concern with combination intravesical regimens is the potential for additive toxicity. In ANZUP 1301, no difference in overall safety was observed between the treatment arms. Serious adverse events were predominantly driven by BCG-related toxicity, with no new safety signals attributable to mitomycin.
Notably, treatment-attributable serious adverse events occurred less frequently in the BCG+MM arm (20%) compared with the BCG-alone arm (32%). While the study was not powered to detect differences in uncommon safety events, these findings support the conclusion that synchronous mitomycin did not worsen the safety profile of BCG-based therapy and may improve it.
Tolerability and treatment completion
One of the most clinically relevant findings from ANZUP 1301 is that the BCG+MM regimen resulted in higher treatment completion rates, suggesting improved tolerability. Higher completion rates alone represent a meaningful outcome in NMIBC, where cumulative toxicity frequently limits delivery of planned therapy. Detailed quality of life data based on patient-reported outcome measures will be presented at EAU26 in March.
Importantly, despite higher completion rates, overall BCG utilisation was substantially lower in the combination arm, highlighting the efficiency of this approach.
Signals in higher-risk disease
Exploratory subgroup analyses showed that patients with higher-risk disease (T1 or any CIS as compared to HGTa only) may have derived particular benefit from combination therapy. While these findings must be interpreted cautiously and do not establish superiority, they raise the possibility that combination intravesical chemo-immunotherapy may be more effective in biologically aggressive disease.
A pragmatic solution to BCG supply constraints
BCG+MM required 39% less BCG than standard BCG therapy. Although treatment decisions should not be driven solely by supply considerations, the reality of ongoing global BCG shortages cannot be ignored. A regimen that preserves oncologic efficacy, improves treatment delivery, and substantially reduces BCG utilisation represents a pragmatic and scalable solution for health systems worldwide.
Implications for clinical practice
ANZUP 1301 did not establish superiority of BCG plus mitomycin over BCG alone. What it did show is arguably as important: that combination therapy delivered similar cancer control, with higher treatment completion rates and significant BCG sparing.
For clinicians managing high-risk NMIBC, these findings challenge the assumption that BCG monotherapy must remain the default approach for all patients. BCG+MM represents a good alternative to BCG monotherapy.
Written by:
- Prof Dickon Hayne, UWA Medical School, University of Western Australia, Perth, WA, Australia ; South Metropolitan Health Service, Murdoch, WA, Australia
- Prof Martin R. Stockler, NHMRC Clinical Trials Centre, University of Sydney, Sydney, Australia; Department of Urology, Concord Repatriation General Hospital, Sydney, NSW, Australia.