I had the privilege to present the results of the DISCUS trial. The DISCUS was an academic investigator initiated international trial conducted in three countries – the UK, France and Spain – in patients with first-line metastatic urothelial carcinoma in whom we compared three versus six cycles of up-front platinum-based chemotherapy before offering two years of avelumab. The design of the DISCUS trial was based on a randomised head-to-head comparison between three cycles of up-front platinum-based chemotherapy, GemCis or GemCarbo, depending on the choice of the investigator, followed by avelumab maintenance up to two years versus the standard arm with six cycles of platinum-based chemotherapy followed by avelumab for up to two years.
Patients needed to have metastatic urothelial carcinoma with an adequate performance status – ECOG 0, 1 or 2 – platinum eligible and eligible also to receive immunotherapy. There were two stratification factors – patients were stratified according to the prognosis, depending on if they had liver metastases, and the choice of chemotherapy the investigator decided. The primary endpoints were two. The first one, the most important one, was the quality of life. The mean change in the quality of life of patients in between the baseline versus the completion of cycle 6 or the equivalent timepoint in the three cycles of chemotherapy only arm. The second primary endpoint was overall survival but the alpha allocation was very small – only 2%.
In the baseline characteristics both arms were very well balanced for the most important clinical factors for prognosis and in terms of the outcome of the trial the DISCUS trial was positive. We met the primary endpoint, those patients randomised to receive three cycles of platinum-based chemotherapy only had better quality of life than those patients who were recruited to the standard six cycles arm.
In terms of number of patients getting better in terms of quality of life, more patients in the three cycles arm got better. In terms of number of patients who got worse in terms of quality of life, more patients got worse in the six cycles arm. Unfortunately, the time to deterioration was not statistically significant, there was a trend to improved for those patients in the three cycles arm but no statistical significance was met. The hazard ratio was 0.81. Interestingly, the quality of life got separated from the early beginning since patients stopped receiving chemotherapy in the three cycles arm the quality of life improved and that difference was maintained over time in the questionnaires of quality of life that we measured.
In terms of activity we saw, and this is very interesting, almost the same, very similar – 61% versus 59% of patients that are responding as best response. Interestingly, and I think for daily practice it’s relevant, no more patients with primary progressions were observed in the short cycles, in three cycles – 6% versus 10% of primary progression in the six cycles arm. In terms of progression free survival the hazard ratio was almost one, 1.05, no statistical differences at all. In terms of overall survival the hazard ratio was 1.15, so that means that three cycles is not better than six cycles but we cannot claim for the non-inferiority because of the design of the trial.
So, in conclusion, the DISCUS trial is really practice changing because three cycles only of platinum-based chemotherapy up front before offering avelumab maintenance has better quality of life than six cycles. Now we don’t really need to squeeze the chemotherapy and to go beyond three cycles. No major differences in terms of efficacy, in terms of responses, in terms of progression free or overall survival was seen but non-inferiority cannot be claimed because of the design of the trial.
The last point, and I think very relevant, with the DISCUS trial we demonstrated that we can run academic trials showing that de-escalation can be feasible, can be done in patients with metastatic urothelial carcinoma even in the era of antibody-drug conjugates.
