Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial.
(2025) Journal for immunotherapy of cancer — Vol. 13, n° 5 (2025), p. e012045 (2025)
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Blanc, Jérémy 
- Abstract
- 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. 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). 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. 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. NCT03674424.
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Blanc, J., Carnot, A., Barthélémy, P., Casert, V., Sautois, B., Van den Brande, J., Vanhaudenarde, V., Staudacher, L., Seront, E., Debien, V., Ameye, L., Kotecki, N., Rothé, F., Rorive, S., Fantoni, J.-C., Tricard, T., Roumeguère, T., Awada, A., & Martinez Chanza, N. (2025). Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial. Journal for immunotherapy of cancer, 13(5 (2025)), e012045. https://doi.org/10.1136/jitc-2025-012045 (Original work published 2025)