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

person Jeremy Blanc Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium info_outline Jeremy Blanc, Aurélien Carnot, Philippe Barthelemy, Vinciane Casert, Lionel Staudacher, Jan Van den Brande, Brieuc Sautois, Vincent Vanhaudenarde, Emmanuel Seront, Veronique Debien, Lieveke Ameye, Nuria Kotecki, Jean Christophe Fantoni, Thibault Tricard, Thierry Andre Roumeguere, Ahmad Awada, Nieves Martinez Chanza

Authors person Jeremy Blanc Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium info_outline Jeremy Blanc, Aurélien Carnot, Philippe Barthelemy, Vinciane Casert, Lionel Staudacher, Jan Van den Brande, Brieuc Sautois, Vincent Vanhaudenarde, Emmanuel Seront, Veronique Debien, Lieveke Ameye, Nuria Kotecki, Jean Christophe Fantoni, Thibault Tricard, Thierry Andre Roumeguere, Ahmad Awada, Nieves Martinez Chanza Organizations Institut Jules Bordet, Hôpital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles, Brussels, Belgium, Centre Oscar Lambret, Lille, France, Medical Oncology, Institut de Cancérologie Strasbourg Europe, Strasbourg, France, Centre Hospitalier Universitaire de Ambrois Paré, Mons, Belgium, Hôpital Paris Saint-Joseph, Paris, France, University Hospital Antwerp, Edegem, Belgium, University Hospital of Liège, CHU Sart-Tilman, Liège, Belgium, CHU UCL Namur, Vezin, Belgium, Institut Roi Albert II, Cliniques universitaires Saint Luc, Université Catholique de Louvain, Brussel, Belgium, Institut Jules Bordet, Anderlecht, Belgium, Université Libre de Bruxelles (ULB), Hôpital Universitaire de Bruxelles (HUB), Institut Jules Bordet, Brussels, Belgium, Hôpitaux Universitaires de Strasbourg, Strasbourg, France, Erasme Hospital, Hopital Universitaire de Bruxelles (HUB), Université Libre de Bruxelles (ULB), Brussels, Belgium Abstract Disclosures Research Funding Aspirant F.R.S.-FNRS (Fonds de la Recherche Scientifique) Merck N.V.-S.A., Overijse, Belgium, an affiliate of Merck KGaA, Darmstadt, Germany, as part of an alliance between Merck KGaA and Pfizer 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. DFS and OS for each treatment arm. ddMVAC - A CG - A PG - A A 12-month DFS 97% (95% CI, 83-100%) 86% (95% CI, 70-94%) 52% (95% CI, 32-69%) 68% (95% CI, 47-82%) 36-month DFS 77% (95% CI, 55-89%) 68% (95% CI, 46-82%) - - 12-month OS 95% (95% CI, 81-99%) 84% (95% CI, 67-92%) 67% (95% CI, 46-81%) 75% (95% CI, 55-87%) 36-month OS 87% (95% CI, 68-95%) 61% (95% CI, 40-76%) - -

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