Rodríguez-Moreno, Juan F.de Velasco, GuillermoÁlvarez-Fernández, CarlosCollado, RicardoFernández, RicardoVázquez, SergioVirizuela, Juan A.Gajate, PabloFont, AlbertLainez, NuriaSevillano-Fernández, ElenaGraña-Castro, OsvaldoBeltrán, LuisMadurga, RodrigoMadurga, RodrigoRodríguez-Antona, CristinaBerraondo, PedroRuiz-Llorente, SergioGarcía-Donas, Jesús2025-12-222025-12-222025-05-01Rodríguez-Moreno, J F, de Velasco, G, Álvarez-Fernández, C, Collado, R, Fernández, R, Vázquez, S, Virizuela, J A, Gajate, P, Font, A, Lainez, N, Sevillano-Fernández, E, Graña-Castro, O, Beltrán, L, Madurga, R, Rodríguez-Antona, C, Berraondo, P, Ruiz-Llorente, S & García-Donas, J 2025, 'Treatment Efficacy and Molecular Dynamics of Neoadjuvant Durvalumab and Olaparib in Resectable Urothelial Bladder Cancer : The NEODURVARIB Trial', Clinical Cancer Research, vol. 31, no. 9, pp. 1644-1656. https://doi.org/10.1158/1078-0432.CCR-24-28901078-0432PubMedCentral: PMC12010967https://hdl.handle.net/10641/6868Publisher Copyright: ©2025 The Authors.Purpose: Neoadjuvant treatment of bladder cancer is evolving, with immunotherapy demonstrating promising activity. PARP inhibition combined with immune activation has been proposed as a synergistic strategy. We conducted a comprehensive molecular characterization of tumors treated with this combination in the neoadjuvant setting to provide crucial results for rational development. Patients and Methods: A phase II clinical trial was designed to evaluate the combination of anti-PDL1 inhibitor durvalumab and PARP inhibitor olaparib, focusing on biomarker dynamics in both pre- and post-treatment settings. A total of 29 patients were enrolled. Genomic and transcriptomic profiling, as well as analyses of immune cell populations, was conducted at baseline and at the time of cystectomy. Results: Of the 29 patients treated, a pathologic complete response was observed in 13 cases (44.8%). No major safety concerns were associated with the treatment, and 26 patients (90%) underwent cystectomy. Mutational patterns, tumor mutation burden, and homologous recombination deficiency remained stable throughout treatment and were not predictive of outcomes. However, a shift toward stromal phenotypes and increased expression of epithelial–mesenchymal transition signatures were observed following therapy, particularly in resistant tumors. Moreover, an increase in circulating CD4+ CD27- CD28- T cells was noted among responders. Conclusions: The combination of neoadjuvant durvalumab and olaparib shows therapeutic activity in bladder cancer. Resistance mechanisms seem to be driven by transcriptional adaptations rather than the emergence of new mutations.135935684enghttp://creativecommons.org/licenses/by-nc-nd/4.0/General MedicineSDG 3 - Good Health and Well-beingClinical Trial, Phase IIJournal ArticleMulticenter StudyYesyesjournal articleopen access10.1158/1078-0432.CCR-24-2890https://www.scopus.com/pages/publications/105004570782https://www.scopus.com/pages/publications/105004570782#tab=citedBy