Journal Article

Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial

Seront, Emmanuel, Casert, Vinciane, Van den Brande, Jan, Barthélémy, Philippe, Roumeguère, Thierry, Kotecki, Nuria, Carnot, Aurélien, Ameye, Lieveke, Fantoni, Jean-Christophe, Awada, Ahmad, Blanc, Jérémy, Martinez Chanza, Nieves, Staudacher, Lionel, Rothé, Françoise, Vanhaudenarde, Vincent, Rorive, Sandrine, Tricard, Thibault, Debien, Veronique, Sautois, Brieuc

2025

Overview

BackgroundImmunotherapy is becoming a standard of care for non-metastatic muscle-invasive bladder cancer (MIBC). The optimal chemotherapy partner for chemo-immunotherapy combinations remains unknown. We evaluated the efficacy and safety of neoadjuvant avelumab-based regimens in patients with MIBC.MethodsThe multicenter phase 2 AURA trial (NCT03674424) enrolled patients with non-metastatic MIBC undergoing radical cystectomy. Cisplatin-eligible patients were randomized to receive avelumab with either dose-dense methotrexate-vinblastine-doxorubicin-cisplatin (ddMVAC-A) or gemcitabine-cisplatin (GC-A). Cisplatin-ineligible patients received either avelumab alone (A) or combined with paclitaxel-gemcitabine (PG-A). The primary endpoint was pathological complete response (pCR). Secondary endpoints included safety, event-free survival, and overall survival (OS).ResultsBetween July 2018 and September 2021, 137 eligible patients were enrolled in the trial. In the cisplatin-eligible cohort (n=79), pCR rates were 58% (95% CI: 42% to 72%) in the ddMVAC-A arm and 53% (95% CI: 37% to 68%) in the GC-A arm. The 36-month OS rates were 87% (95% CI: 76% to 98%) for ddMVAC-A and 67% (95% CI: 53% to 84%) for GC-A. In the cisplatin-ineligible cohort (n=58), pCR rates were 14% (95% CI: 6% to 31%) in the PG-A arm and 32% (95% CI: 18% to 51%) in the A arm. The 36-month OS rates were 48% (95% CI: 33% to 71%) for PG-A and 42% (95% CI: 27% to 65%) for A. Overall, 51 (38%) patients experienced grade 3–4 treatment-related adverse events.ConclusionsAvelumab combined with cisplatin-based neoadjuvant chemotherapy showed promising efficacy in MIBC with a favorable safety profile, also with the ddMVAC regimen. Among cisplatin-ineligible patients, avelumab monotherapy showed encouraging activity, with no additional benefit observed from the PG-A regimen. These results support the use of the ddMVAC regimen as a potential chemotherapy partner for neoadjuvant chemo-immunotherapy combinations in future phase 3 trials, providing an alternative to the GC regimen currently under investigation.Trial registration number NCT03674424.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adjuvants / Aged / Aged, 80 and over / Antibodies, Monoclonal, Humanized / Antibodies, Monoclonal, Humanized - administration & dosage / Antibodies, Monoclonal, Humanized - pharmacology / Antibodies, Monoclonal, Humanized - therapeutic use / Antineoplastic Combined Chemotherapy Protocols / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / avelumab / Bladder Cancer / Cancer Research / Cancer therapies / Chemotherapy / Cisplatin / Cisplatin - administration & dosage / Clinical Cancer Immunotherapy / Clinical trials / Deoxycytidine / Deoxycytidine - administration & dosage / Deoxycytidine - analogs & derivatives / Female / Gemcitabine / Genitourinary Cancer / Human health sciences / Humans / Hypotheses / Immune Checkpoint Inhibitor / Immune checkpoint inhibitors / Immunology / Immunology and Allergy / Immunotherapy / Lymphatic system / Male / Metastasis / Middle Aged / Molecular Medicine / Neoadjuvant / Neoadjuvant Therapy / Neoadjuvant Therapy - methods / Neoplasm Invasiveness / Oncologie / Oncology / Original Research / Pharmacology / Sciences de la santé humaine / Software / Survival analysis / Urinary Bladder Neoplasms / Urinary Bladder Neoplasms - drug therapy / Urinary Bladder Neoplasms - mortality / Urinary Bladder Neoplasms - pathology / Urological surgery