As we all know, BCG failure is a very difficult situation to handle. Radical cystectomy is the gold standard but we see emerging treatments about bladder-preserving strategies. So we made a simple hypothesis – that if we use intravesical immunotherapy we would have good results in this setting of patients. So we used intravesical administration of durvalumab in BCG refractory patients.
It was actually a phase I/II trial. It included an initial phase I to develop the maximum tolerated dose. This phase ran smoothly; we started at 500mg and we went up to 1000mg with no dose limiting toxicities. Then the phase II was the actual part of the study where we gave the drug to BCG refractory patients.
The results are actually very promising. Our primary endpoint, which was the one-year high grade relapse free, was 38.5% which is actually very good. The one-month high grade recurrence free was 100% and the six-month high grade recurrence free rate was 50%. The most important is that the durvalumab intravesically administered was very well tolerated; we had no grade 3 or above toxicities and it was easy to handle from our part and from the patient’s part.
How can the study results impact clinical practice?
We need more studies in this setting. Single-arm studies may not be efficient. We know that the FDA approves drugs based on single-arm studies. I think we will develop several modalities in order to preserve bladders in this setting of patients.