{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T22:19:29Z","timestamp":1783635569909,"version":"3.55.0"},"reference-count":27,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"20","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2026,7,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>To evaluate the efficacy and safety of neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) combined with durvalumab \u00b1 tremelimumab in patients with muscle-invasive bladder cancer (MIBC).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      NEMIO (ClinicalTrials.gov identifier:\n                      <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\/ct2\/show\/NCT03549715\">NCT03549715<\/jats:ext-link>\n                      ) is a multicenter, randomized, noncomparative phase II trial in cT2-T4a N0-1 cisplatin-eligible MIBC planned for radical cystectomy (RC). Patients received ddMVAC (cisplatin 70 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , methotrexate 30 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , doxorubicin 30 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      , and vinblastine 3 mg\/m\n                      <jats:sup>2<\/jats:sup>\n                      on days 1, and pegfilgrastim 6 mg on days 2) once every 2 weeks \u00d7 four cycles plus durvalumab \u00b1 tremelimumab (durvalumab 1,500 mg and tremelimumab 75 mg) once every 4 weeks \u00d7 two doses (C1D1 and C3D1) before RC. Coprimary end points (local assessment) were pathologic complete response (pCR; ypT0N0) and grade \u22653 treatment-related adverse events (TRAEs). The study was considered positive if the pCR rate was \u226545% and the rate of grade \u22653 TRAEs was \u226430%.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>From 2018 to 2022, 119 patients received ddMVAC + durvalumab (n = 60) or ddMVAC + durvalumab + tremelimumab (n = 59); 113 underwent RC. The overall Bayesian posterior mean pCR rate was 48.70% (95% CI, 35.93 to 61.56) with doublet and 46.27% (95% CI, 33.92 to 58.85) with triplet. Among 103 patients with PD-L1 data (exploratory), Bayesian posterior mean pCR was 68.25% (95% CI, 54.57 to 80.49) in PD-L1\u2013high tumors versus 33.49% (95% CI, 22.13 to 45.91) in PD-L1\u2013low\/negative tumors. Bayesian posterior mean grade \u22653 TRAEs occurred in 40.95% (95% CI, 32.50 to 49.69) overall (30.48% [95% CI, 20.00 to 42.08] doublet; 49.63% [95% CI, 37.55 to 61.73] triplet); immune-related adverse events occurred in 26.9% (grade \u22653 4.2%). Two-year event-free survival and overall survival rates were 75% and 85% in the doublet arm, and 77% and 88% in the triplet arm, respectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Neoadjuvant ddMVAC plus durvalumab demonstrated encouraging pCR rates, favorable early survival outcomes, and manageable safety profile. Adding tremelimumab provides similar pCR but worse toxicity. These results support further study of ddMVAC plus durvalumab as a neoadjuvant chemoimmunotherapy strategy for localized MIBC, to be evaluated in comparative trials within an evolving perioperative treatment landscape.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-03045","type":"journal-article","created":{"date-parts":[[2026,5,26]],"date-time":"2026-05-26T19:59:23Z","timestamp":1779825563000},"page":"1921-1932","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Neoadjuvant Durvalumab \u00b1 Tremelimumab in Combination With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin in Muscle-Invasive Bladder Carcinoma: Results of the Phase I\/II NEMIO Study"],"prefix":"10.1200","volume":"44","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9082-1341","authenticated-orcid":false,"given":"Constance","family":"Thibault","sequence":"first","affiliation":[{"name":"Department of Medical Oncology, H\u00f4pital Europ\u00e9en Georges Pompidou, AP-HP, Paris Cit\u00e9 University, Paris, France"},{"name":"Institut du Cancer Paris CARPEM, AP-HP Centre, Paris Cit\u00e9 University, Paris, France"},{"name":"INSERM UMR-S 1147, University of Paris Cit\u00e9, Centre de Recherche des Cordeliers, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mostefa","family":"Bennamoun","sequence":"additional","affiliation":[{"name":"Oncology Department, Institute Curie, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aude","family":"Fl\u00e9chon","sequence":"additional","affiliation":[{"name":"Oncology Department, Centre L\u00e9on B\u00e9rard, Lyon, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3127-1554","authenticated-orcid":false,"given":"Gwenaelle","family":"Gravis","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Institut Paoli-Calmettes, Aix-Marseille Univ, INSERM, CNRS, CRCM, Immunity and Cancer Team, Marseille, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4030-8299","authenticated-orcid":false,"given":"Damien","family":"Pouessel","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, Oncopole Claudius Regaud, IUCT-Oncopole, Toulouse, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7321-7345","authenticated-orcid":false,"given":"Pierre","family":"Combe","sequence":"additional","affiliation":[{"name":"Medical Oncology Department, VIVALTO Sant\u00e9, P\u00f4le Sant\u00e9 L\u00e9onard de Vinci, Chambray-l\u00e8s-tours, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Delphine","family":"Borchiellini","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology, Centre Antoine Lacassagne, Universit\u00e9 C\u00f4te d'Azur, Nice, 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