{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T21:11:39Z","timestamp":1792876299890,"version":"4.5.0"},"reference-count":40,"publisher":"BMJ","issue":"5","license":[{"start":{"date-parts":[[2025,5,25]],"date-time":"2025-05-25T00:00:00Z","timestamp":1748131200000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Association Jules Bordet","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}]},{"DOI":"10.13039\/100020956","name":"Merck Healthcare KGaA","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/100020956","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Institut Jules Bordet","award":["Sponsor"],"award-info":[{"award-number":["Sponsor"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Immunother Cancer"],"accepted":{"date-parts":[[2025,5,7]]},"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      The multicenter phase 2 AURA trial (\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03674424\">NCT03674424<\/jats:ext-link>\n                      ) 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).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u20134 treatment-related adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Trial registration number<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03674424\">NCT03674424<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jitc-2025-012045","type":"journal-article","created":{"date-parts":[[2025,5,24]],"date-time":"2025-05-24T21:25:23Z","timestamp":1748121923000},"page":"e012045","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":11,"title":["Avelumab-based neoadjuvant therapy in patients with muscle-invasive bladder cancer (AURA Oncodistinct-004): a phase 2 multicenter clinical trial"],"prefix":"10.1136","volume":"13","clinical-trial-number":[{"clinical-trial-number":"nct03674424","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03674424","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct03674424","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-0056-7898","authenticated-orcid":false,"given":"J\u00e9r\u00e9my","family":"Blanc","sequence":"first","affiliation":[{"name":"Medical Oncology Department, Institut Jules Bordet, H\u00f4pital Universitaire de Bruxelles, Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aur\u00e9lien","family":"Carnot","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Centre Oscar Lambret, Lille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Barth\u00e9l\u00e9my","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, ICANS, Strasbourg, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinciane","family":"Casert","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Centre Hospitalier Universitaire Ambroise Par\u00e9, Mons, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brieuc","family":"Sautois","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, CHU de Li\u00e8ge H\u00f4pital du Sart Tilman, Li\u00e8ge, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Van den Brande","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, University Hospital Antwerp, Edegem, 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