We know that BCG has been the mainstay of treatment for high-risk non-muscle-invasive bladder cancer for almost half a century. There’s a current global BCG shortage, and we’re obviously looking for alternatives that may be more efficacious or might have lower side effect profiles in the treatment of high-risk non-muscle-invasive bladder cancer.
There is some evidence already existing suggesting benefits of the addition of chemotherapy to BCG immunotherapy, but this hasn’t really been tested in a large phase III randomised trial.
What was the methodology?
We performed an open-label, phase III randomised trial with patients with high-risk non-muscle-invasive bladder cancer to test the addition of mitomycin to BCG to look for efficacy and safety compared to BCG induction and maintenance alone.
Patients with papillary bladder cancer, stages Ta or T1 including concomitant CIS but not with pure CIS, were randomised 1:1 to either receive BCG plus mitomycin or BCG alone.
Blinding wasn’t possible for the study because the agents look different, and also the treatment schedules and safety precautions were different.
What did you find?
We randomised 500 patients to the study from 16 Australian and one UK-based centre. We found that the BCG plus mitomycin had very similar efficacy and safety to BCG but with fewer treatment discontinuations. Furthermore, 40% fewer doses of BCG were required in those in the combination arm than those with BCG alone. A post hoc subgroup analysis further suggested that in the higher-risk patients – so in other words those patients with T1 or carcinoma in situ – versus the lower risk patients, did seem to do better in terms of the addition of mitomycin.
Really, in conclusion, we think that BCG plus mitomycin is a very good alternative to BCG alone. With the current global BCG shortage, wide adoption of the BCG plus mitomycin regimen, could resolve this BCG shortage.
What are the clinical implications of these findings?
The findings suggest a treatment which is similarly tolerated and similarly efficacious, maybe a little bit better, but with using a lot less BCG which is basically unavailable. Best estimates are that there’s about a 30-50% shortfall of BCG globally, so it would certainly address that situation, as well as being well-tolerated and efficacious.
Is there anything else you would like to add?
This is an ANZUP trial, so ANZUP is a collaborative trials organisation from Australia and New Zealand. The actual study was coordinated by the clinical trials centre at the University of Sydney, and it was all academically sponsored investigator-initiated study, so the funding came from Cancer Australia, NHMRC, and ANZUP’s Below the Belt.
We’re grateful to MSD for ensuring [??] BCG supply during the study during a global shortage. We got some discounted mitomycin from OmegaPharm. Really, my thanks go to all the many clinicians, clinical trial staff, and allied health professionals who helped us to complete this major randomised trial – one of the largest non-muscle-invasive bladder cancer trials that’s been completed for many years. But of course the people to really thank are the participants in the study itself.
