ESMO 2025 | DISCUS: comparing 3 vs 6 chemotherapy cycles before avelumab in aUC

In the DISCUS trial, the design was one-to-one. Patients were randomized to receive standard six cycles of platinum-based chemotherapy. According to the investigator’s decision, they could go for GEM-CARBO or GEM-TAX before offering avelumab maintenance for up to two years versus the experimental arm, diminishing the number of cycles, only three cycles of platinum-based chemotherapy before starting a volume of maintenance. Patients were stratified according to two factors. The first one, liver metastasis, yes or no. Second one, the choice of platinum-based chemotherapy, cisplatin or carboplatin. The primary endpoint is important here because that was patient-focused and it was the quality of life of the patient in between the baseline versus the completion of cycle six in the standard arm six cycles or the equivalent time point in the three cycles arm. The primary outcomes that we have is that we met the primary endpoint. So our patients at DISCUS demonstrated that the quality of life was better when offering only three cycles of platinum-based chemotherapy instead of the standard six cycles of platinum-based chemotherapy. In terms of the quality of life, we saw that the differences in the quality of life were early separated, the curves, so as soon as the patient stopped the chemotherapy in the three cycles arm, the quality of life improved and that improvement was maintained over time. I think this is relevant and important. In addition, what happened with the efficacy? Because we tried that by shortening the chemotherapy, we were impacting more responses, deeper responses and longer responses translated into better survival. That was not seen at the DISCUS prospective randomized trial. A very similar number of responses, 61% of patients responded in the three cycles only and versus 59% in the six cycles arm. And interestingly, fewer patients progressed as primary, as first response or best response in the three cycles arm only, 6% versus 10% in the six cycles arm. Progression-free survival and overall survival Kaplan-Meier curves largely overlap with a median overall survival in the two groups of 18.9 months, exactly the same, and the hazard ratio was 1.15 for overall survival. We cannot claim non-inferiority because of the limitations of the statistics and the design of the trial, but I think clinically speaking, I think we can say that there is no clear detrimental activity by diminishing the number of cycles.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.