BCG Plus Mitomycin Fails to Improve DFS in ANZUP 1301

Key Takeaways

• BCG plus mitomycin did not show disease-free survival superiority over BCG alone in this randomized phase 3 trial.
• Recurrence and progression events were numerically lower in the combination arm, and other secondary counts were reported for both groups.
• The combination arm used fewer BCG doses, more patients received at least 75% of planned treatment, and grade 3 to 5 adverse events occurred in both groups.

In ANZUP 1301, a randomized phase 3 trial in BCG-naive non-muscle-invasive bladder cancer, intravesical BCG plus mitomycin was not superior to BCG alone for the primary disease-free survival endpoint.

After maximal transurethral resection, 2-year disease-free survival was 75% with the combination and 71% with BCG alone. The study evaluated patients with high-grade pTa or any-grade pT1 disease, with concurrent carcinoma in situ allowed.

Investigators randomly assigned 501 participants in a 1:1 ratio after maximal transurethral resection, with 249 allocated to BCG plus mitomycin and 252 to BCG alone. Eligibility required high-grade pTa or any-grade pT1 non–muscle-invasive bladder cancer, and concurrent carcinoma in situ was permitted. Across the enrolled cohort, 53% had pTa disease, 47% had pT1 disease, and 28% had concurrent carcinoma in situ. This was a parallel-group trial in a BCG-naive cohort, with a median follow-up of 48 months.

Disease-free survival was the primary endpoint, and the comparison yielded a hazard ratio of 0.87 with a 95% confidence interval of 0.65 to 1.16. The p value was 0.3, and the investigators concluded that BCG plus mitomycin was not proved superior to BCG alone. Secondary counts were 214 versus 210 for complete response at 3 months and 79 versus 86 for recurrence. Progression events were 28 versus 44, and deaths were 26 versus 23. Overall, the efficacy findings did not show superiority for the combination on the primary endpoint.

Treatment delivery differed between groups, with more total instillations in the combination arm but fewer BCG doses overall. Investigators reported 4033 versus 3383 instillations, 2056 versus 3383 total BCG doses, and median BCG exposure of 9 versus 16 doses. At least 75% of planned doses were received by 78% versus 68% of participants, with a reported p value of 0.02. The researchers also noted 39% fewer BCG doses and fewer treatment discontinuations with the combination, while grade 3 to 5 adverse events were 43 versus 37. Serious adverse events were reported in both arms.

The authors described BCG plus mitomycin as a pragmatic alternative rather than a superior regimen. They also linked reduced BCG use to the setting of global BCG shortage. Their framing centered on treatment pragmatism, not on a claim of better cancer control.