Treatment Efficacy and Molecular Dynamics of Neoadjuvant Durvalumab and Olaparib in Resectable Urothelial Bladder Cancer: The NEODURVARIB Trial
Year: 2025
Type: article
Study design: Clinical Trial
Abstract: 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.
Source: Clinical Cancer Research
Authors: Juan F. Rodríguez-Moreno, Guillermo de Velasco, Carlos Álvarez-Fernández, Ricardo Collado, Ricardo Fernández, Sergio Vázquez, Juan A. Virizuela, Pablo Gajate, Albert Font, Nuria Lainez, Elena Sevillano-Fernández, Osvaldo Graña-Castro, Luis Beltrán, Rodrigo Madurga, Cristina Rodríguez-Antona, Pedro Berraondo, Sergio Ruiz-Llorente, Jesús García-Donas
Institutions: Universidad San Pablo CEU, HM Hospitales, Hospital Universitario 12 De Octubre, Hospital Universitario Central de Asturias, Complejo Hospitalario de Cáceres, Hospital de Cruces, Hospital Universitario Lucus Augusti, Hospital Universitario Virgen Macarena, Hospital Universitario Ramón y Cajal, Institut Català d'Oncologia, Complejo Hospitalario de Navarra, National Health Service, Barts Health NHS Trust, Universidad Francisco de Vitoria, Spanish National Cancer Research Centre, Navarre Institute of Health Research, Centro de Investigación Biomédica en Red de Cáncer, Centro de Investigación Médica Aplicada, Universidad de Alcalá, Hospital Universitario HM Sanchinarro
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4409645971