Dr Hayne on the Rationale for Evaluating Mitomycin Plus BCG vs BCG Alone in NMIBC

"For almost half a century, we've seen the benefits of chemoimmunotherapy in lots of other oncologic settings, and [have been] trying to bring that further into the treatment paradigm for high-risk NMIBC. There's been a fair amount of work in this space already…but the technology hasn't really seemed to penetrate globally at all."

Dickon Hayne, MD, FRCS, MBBS, a professor of urology at The University of Western Australia Medical School, as well as a consultant urological surgeon and the head of Urology for the South Metropolitan Health Service, discussed the rationale for conducting the phase 3 ANZUP 1301 trial (NCT02948543) evaluating mitomycin (Zusduri; UGN-102) plus BCG, an alternative to BCG alone in non–muscle-invasive bladder cancer (NMIBC).

Hayne emphasized that BCG has long been the cornerstone of treatment for high-risk NMIBC. However, given the established efficacy of combining chemotherapy and immunotherapy in other oncologic settings, efforts have been made to investigate this approach in NMIBC. Prior studies exploring mitomycin with BCG have produced mixed outcomes. For example, a study using electromotive drug administration of mitomycin showed promising recurrence and survival benefits, but the required technology failed to gain widespread adoption. Similarly, the prospective CUETO 93009 trial demonstrated clinical benefit but was associated with high toxicity, with more than 50% of patients experiencing grade 3 or higher adverse effects, limiting its utility in this population.

Against this backdrop, the ANZUP 1301 trial was designed to determine whether combining mitomycin with BCG could enhance efficacy while maintaining acceptable tolerability. Data from ANZUP, which were presented at the 2025 ASCO Annual Meeting, indicated that the combination demonstrated comparable efficacy and safety to BCG monotherapy, with the added benefit of reducing the total BCG dose by 40%. Notably, subgroup analysis revealed that patients with high-risk NMIBC derived greater benefit from the combination regimen compared with BCG alone.

Hayne concluded that the findings support the feasibility of combining mitomycin with BCG in NMIBC, particularly in high-risk patients, and may help mitigate BCG shortages by reducing required dosing without compromising efficacy. This approach offers a promising alternative strategy for optimizing outcomes in this patient population.