Avelumab as neoadjuvant therapy in patients with urothelial non-metastatic muscle invasive bladder cancer: a multicenter, randomized, non-comparative, phase II study (Oncodistinct 004 - AURA trial)

BMC Cancer

Vinciane Casert¹  Jean Christophe Fantoni²  Aurélien Carnot²  Vincent Vanhaudenarde³  Marco Gizzi⁴  Louisa Soukane⁵  Simone Albisinni⁵  Lionel Staudacher⁶  Stephane Culine⁷  Emmanuel Seront⁸  Thibault Tricard⁹  Philippe Barthelemy⁹  Marianne Paesmans^1,10  Ahmad Awada^1,10  Thierry Gil^1,10  Rafael Caparica^1,10  Thierry Roumeguere^1,11  Nieves Martinez Chanza^1,11  Jan Van den Brande^1,12  Brieuc Sautois^1,13 

[1] Centre Hospitalier Universitaire de Ambrois Paré, Mons, Belgium;Centre Oscar Lambret, Lille, France;Clinique Sainte-Elisabeth, UCL, Namur, Belgium;Grand Hopital de Charleroi, Charleroi, Belgium;Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium;Hopital Paris Saint Joseph, Paris, France;Hopital Saint-Louis, Paris, France;Hopital de Jolimont, Jolimont, Belgium;Institut de Cancérologie Strasbourg Europe ICANS, Strasbourg, France;Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium;Jules Bordet Institute, Université Libre de Bruxelles, Brussels, Belgium;Hopital Erasme, Université Libre de Bruxelles, Brussels, Belgium;University Hospital Antwerp, UZA, Antwerp, Belgium;University Hospital of Liege (CHU Sart Tilman), Liège, Belgium;

关键词: Avelumab;    Bladder cancer;    Checkpoint inhibitor;    Immunotherapy;    Neoadjuvant;    PD-1 blockade;    Urothelial carcinoma;   

DOI  :  10.1186/s12885-021-08990-3

来源: Springer

【 摘 要 】

IntroductionCisplatin-based neoadjuvant chemotherapy (NAC) followed by surgery is the standard treatment for patients with non-metastatic muscle invasive bladder cancer (MIBC). Unfortunately, many patients are not candidates to receive cisplatin due to renal impairment. Additionally, no predictive biomarkers for pathological complete response (pCR) are currently validated in clinical practice. Studies evaluating immune checkpoint inhibitors in the peri-operative setting are emerging with promising results. Clinical trials are clearly required in the neoadjuvant setting in order to improve therapeutic strategies.Methods and analysisOncodistinct 004 – AURA is an ongoing multicenter phase II randomized trial assessing the efficacy and safety of avelumab single-agent or combined to different NAC regimens in patients with non-metastatic MIBC. Patients are enrolled in two distinct cohorts according to their eligibility to receive cisplatin-based NAC. In the cisplatin eligible cohort, patients are randomized in a 1:1 fashion to receive avelumab combined with cisplatin-gemcitabine or with dose-dense methotrexate-vinblastine-doxorubicin-cisplatin. In the cisplatin ineligible cohort, patients are randomized at a 1:1 ratio to paclitaxel-gemcitabine associated to avelumab or avelumab alone. Primary endpoint is pCR. Secondary endpoints are pathological response and safety.Ethics and disseminationThe study is approved by ethics committee from all participating centers. All participants provide informed consent prior inclusion to the study. Once completed, results will be published in peer-reviewed journals.Trial registration numberClinicalTrials.gov (NCT03674424).

【 授权许可】

CC BY