Intravesical IO using durvalumab shows promising results for patients with high risk NMIBC after BCG failure

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Published: 16 Mar 2023
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Dr Charalampos Fragkoulis - General Hospital of Athens, Athens, Greece

Dr Charalampos Fragkoulis speaks to ecancer about a phase II trial by the Hellenic GU Cancer Group.

This trial investigates the intravesical administration of durvalumab to patients with high risk non muscle invasive bladder cancer after BCG failure. The trial was based on the hypothesis that intravesical administration of durvalumab will not be related with severe adverse events.

Dr Fragkoulis says that the study found that intravesical IO using durvalumab is feasible with an excellent safety profile. The trial has paved the way for further study of intravesical IO in high-risk patients with NMIBC after BCG failure.

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.