Testing the safety and efficacy of the PD-L1 antibody durvalumab
Dr Christophe Massard - Institut Gustave Roussy, Paris, France
This year we presented a trial called the MEDI1108 phase I/II trial evaluating durvalumab in different patients with different cancer. The focus of this presentation was bladder cancer patients.
Can you tell us how the patients were selected out of all cancers and then the results that were found with medicine?
In this trial more than 1,000 patients were enrolled with different tumour types and it was decided to dedicate a cohort for patients with bladder cancer. Durvalumab was prescribed in these patients and patients were treated with durvalumab 10mg/kg every two weeks. Patients were evaluated every six weeks and if there was no proliferation the patients were treated for one year. So the main result of the trial was first durvalumab treatment is very well tolerated, the most frequent adverse events were very low grade. There were only three patients with grade 3 and there were no grade 4 and no grade 5.
The second message is that the anti-tumour activity is very important. The objective response rates were 31% in the patients enrolled in the cohort with bladder cancer and in the subgroup of patients with PD-L1 positive expression the objective response rate was 46% versus 0% in the PD-L1 negative subgroup.
Very significant results for the PD-L1 positive count then?
And with these results in mind, are there any plans to escalate or introduce new patients?
The goal of this trial is first to expand the cohort and, based on these very promising results, it was decided to open a future trial. So durvalumab will be evaluated in bladder cancer in first line in a trial called DANUBE in monotherapy or in combination with tremelimumab. The second trial, called BISCAY will evaluate durvalumab in combination with other drugs such as EGFR inhibitors for patients with bladder cancer.
Were there any toxicities in patients with durvalumab as a monotherapy or in any combinations?
In this trial durvalumab was prescribed in monotherapy. The most frequent adverse events were very low grade and the most frequent side effects were fatigue, diarrhoea and loss of appetite. So basically the safety profile of durvalumab was clearly manageable in bladder cancer.
Do you have any thoughts about the ongoing development of PD-L1 as a marker for immunotherapy?
Yes, we know that PD-1, PD-L1 show an activity in bladder cancer. There are several compounds in development such as durvalumab, atezolizumab, nivolumab. We know that there are different assays to evaluate PD-L1 expression, PD-1 expression could be evaluated on TC, tumour cells, or in tumour infiltrating immune cells or both. At this time there is no clear gold standard for evaluation of PD-L1. It’s very good news for patients - clearly five years ago it was nearly impossible to imagine that all these drugs would be available for patients. So it’s good news for patients to have this clinical trial ongoing and it will be probably important to propose this trial for patients.