Double the impact with less BCG: Mitomycin combo maintains efficacy in NMIBC

Combining intravesical Bacillus Calmette-Guérin (BCG) with mitomycin provides similar efficacy and safety compared to BCG alone in participants with high-risk, non-muscle-invasive bladder cancer (NMIBC), while using approximately 40% fewer BCG doses, presenting a potential game-changer amidst a global BCG shortage.

The phase 3 BCG+MM/ANZUP 1301 trial (NCT02948543) results were presented by Prof. Dickon Hayne (University of Western Australia Medical School, Australia) [1]. In this multicentre study, 501 participants with high-grade Ta or any-grade T1 NMIBC were randomised to receive either BCG alone or a combination of BCG and mitomycin. During the 11-week induction phase, the combination group received alternating treatments (BCG on weeks 1, 2, 4, 5, 7, 8; mitomycin on weeks 3, 6, 9), followed by maintenance therapy through 12 months. Treatment response was assessed by cystoscopy and biopsy.

With a median follow-up of 48 months, the 2-year disease-free survival (DFS) was 75% in the combination group versus 71% with BCG alone (HR 0.87; 95% CI 0.65–1.16; P=0.34). The complete response rate at 3 months was 90% versus 86% in the combination arm and BCG alone arm, respectively (relative risk 1.05; 95% CI 0.98–1.12; P=0.22). At 24 months, the recurrence-free survival rates reached 80% for the combination group and 75% for BCG alone (HR 0.85; 95% CI 0.61–1.19). Progression-free survival at the same point amounted to 92% and 90% for the respective groups (HR 0.68; 95% CI 0.41–1.11). At 5 years, overall survival rates were 88% versus 87% (HR 1.06; 95% CI 0.60–1.86; P=0.85).

Subgroup analysis suggested a more substantial DFS benefit with the combination in T1 tumours (HR 0.74; 95% CI 0.49–1.11) compared with Ta tumours (HR 1.00; 95% CI 0.67–1.50). An additional post-hoc stratification by risk showed a DFS benefit for high-risk participants (HR 0.69; 95% CI 0.48–0.99; P=0.043) but not for those with lower risk (HR 1.28; 95% CI 0.79–2.09).

The safety profile of adding mitomycin to BCG was largely favourable. Adverse events (AEs) were comparable between groups, though the combination arm experienced notably fewer flu-like symptoms. While fatigue and urinary and flu-like symptoms were common across both arms, serious AEs were rare and 3 treatment-related deaths were reported: 1 in the combination group, due to a BCG-related mycotic aortic aneurysm, and 2 in the BCG-only group (1 from myocardial infarction and 1 from sepsis).

Importantly, the regimen significantly reduced the use of BCG. The total number of BCG doses administered in the combination group was 2,056, compared with 3,383 in the monotherapy group. Median BCG doses per participant were 9 and 16, respectively. More participants in the combination group completed over 75% of their planned treatments (78% vs 68%; P=0.02), and full completion rates were also higher (75% vs 64%).

“The BCG shortage is a real and growing concern globally,” elaborated invited discussant Dr John Sfakianos (Mount Sinai, NY, USA). “This combination is well-tolerated and as effective as BCG alone. It’s a regimen I will likely adopt in my practice. This study is clinically significant and deserves wide recognition.”

1. Hayne D, et al. Mitomycin plus BCG as adjuvant intravesical therapy for high-risk, non–muscle-invasive bladder cancer: A randomized phase 3 trial (ANZUP 1301). Abstract LBA4504, ASCO Annual Meeting 2025, 30 May–3 June, Chicago, IL, USA.

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Posted on 30 July 2025