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Publications

Journal Article Clinical Trial, Phase II Multicenter Study Randomized Controlled Trial Epublish

PubMed: 40413024 DOI: 10.1136/jitc-2025-012045

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

J Immunother Cancer 13(5)

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

Affiliations

  • Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
  • Medical Oncology Department, Centre Oscar Lambret, Lille, France.
  • Medical Oncology Department, ICANS, Strasbourg, France.
  • Medical Oncology Department, Centre Hospitalier Universitaire Ambroise Paré, Mons, Belgium.
  • Medical Oncology Department, CHU de Liège Hôpital du Sart Tilman, Liège, Belgium.
  • Medical Oncology Department, University Hospital Antwerp, Edegem, Belgium.
  • Medical Oncology Department, CHU UCL Namur, Namur, Belgium.
  • Medical Oncology Department, Hôpital Paris Saint-Joseph, Paris, France.
  • Medical Oncology Department, Cliniques universitaires Saint-Luc, Brussels, Belgium.
  • Clinical Trials Center, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
  • Breast Cancer Translational research Laboratory, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
  • Pathology Department, CurePath, Jumet, Belgium.
  • Urology Department, Centre Hospitalier Universitaire de Lille, Lille, France.
  • Urology Department, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.
  • Urology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
  • Urology Department, Hôpital Erasme, Hôpital Universitaire de Bruxelles, Brussels, Belgium.
  • Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium.

Abstract

BACKGROUND

Immunotherapy 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.

METHODS

The 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).

RESULTS

Between 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.

CONCLUSIONS

Avelumab 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.

MeSH

Urinary Bladder, Urinary Bladder Neoplasms, Safety, Muscles, Neoplasms, Drug Therapy, Immunotherapy, Neoadjuvant Therapy, Therapeutics, Chemotherapy