Avelumab (A) as neoadjuvant therapy in patients (pts) with muscle-invasive urothelial carcinoma (MIUC): Survival data of AURA trial, Oncodistinct 004.

4516 Background: Immunotherapy in the perioperative setting of MIUC appears promising. The AURA trial (NCT03674424) investigated the addition of avelumab to neoadjuvant dose-dense MVAC (ddMVAC) or cisplatin-gemcitabine (CG) respectively, followed by surgery in the cisplatin-eligible cohort. The primary endpoint was previously reported with high pathological complete response (pCR) rates with each cisplatin-based regimen. In the cisplatin-ineligible cohort, pts were randomized to neoadjuvant A alone or in combination with paclitaxel-gemcitabine (PG) followed by surgery. Avelumab monotherapy showed encouraging pCR but the addition of PG did not provide any benefit. Here, we report the survival data from cisplatin-eligible and ineligible cohorts of the AURA trial. Methods: In the cisplatin-eligible cohort, 79 pts were randomly assigned to the ddMVAC-A (n=39) or CG-A (n=40) groups. In the cisplatin-ineligible cohort, 58 pts were randomly assigned to the PG-A (n=29) or A (n=29) groups. Disease-free survival (DFS) and overall survival (OS) were estimated using the Kaplan-Meier method at 12 months and 36 months for the overall cohort and by subgroups. Results: Median follow-up was 33 months and 45 deaths were reported. In the cisplatin-eligible cohort, 12-month DFS was 92% (95% CI, 83-96%) and 36-month DFS was 72% (95% CI, 57-83%). For ddMVAC-A group: 97% and 77%, respectively. For CG-A group: 86% and 68%. Overall, 12-month OS was 89% (95% CI, 80-95%) and 36-month OS was 73% (95% CI, 61-83%). For ddMVAC-A: 95% and 87%. For CG-A: 84% and 61%. Among the ypT0N0 pts, no events were registered within 12 months of follow-up showing a DFS rate of 100% for both arms. At 36 months no events were reported for pts treated with ddMVAC-A and two for CG-A showing DFS rates of 100% and 78% respectively. In the cisplatin-ineligible cohort, 12-month DFS was 60% (95% CI, 46-72%) and 12-month OS was 71% (95% CI, 57-81%). For PG-A: 52% and 67%. For A: 68% and 75%. Among the ypT0N0 pts, no DFS events occurred within 12 months. Data for 36-month are not yet mature. Overall, the main cause of death was disease progression (73%). Conclusions: The addition of neoadjuvant avelumab to cisplatin-based chemotherapy results in a high DFS and OS at 12 and 36 months respectively, especially in pts with complete response to neoadjuvant treatment. Combination with ddMVAC regimen offers robust activity. Cisplatin-ineligible pts had lower survival outcomes with no benefit of PG addition. Clinical trial information: NCT03674424 . Table: see text