[en] [en] BACKGROUND: 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.
METHODS: The multicenter phase 2 AURA trial (NCT03674424) 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).
RESULTS: 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 3-4 treatment-related adverse events.
CONCLUSIONS: 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.
TRIAL REGISTRATION NUMBER: NCT03674424.
Disciplines :
Oncology
Author, co-author :
Blanc, Jérémy ; Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Carnot, Aurélien; Medical Oncology Department, Centre Oscar Lambret, Lille, France
Barthélémy, Philippe; Medical Oncology Department, ICANS, Strasbourg, France
Casert, Vinciane; Medical Oncology Department, Centre Hospitalier Universitaire Ambroise Paré, Mons, Belgium
Sautois, Brieuc ; Université de Liège - ULiège > Département de pharmacie
Van den Brande, Jan; Medical Oncology Department, University Hospital Antwerp, Edegem, Belgium
Vanhaudenarde, Vincent; Medical Oncology Department, CHU UCL Namur, Namur, Belgium
Staudacher, Lionel; Medical Oncology Department, Hôpital Paris Saint-Joseph, Paris, France
Seront, Emmanuel; Medical Oncology Department, Cliniques universitaires Saint-Luc, Brussels, Belgium
Debien, Veronique; Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Ameye, Lieveke ; Clinical Trials Center, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Kotecki, Nuria; Medical Oncology Department, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Rothé, Françoise; Breast Cancer Translational research Laboratory, Institut Jules Bordet, Hôpital Universitaire de Bruxelles, Brussels, Belgium
Association Jules Bordet Merck KGaA Institut Jules Bordet
Funding text :
The authors thank all patients, their families and caregivers for participating in the AURA trial. We thank the Jules Bordet Institute as sponsor of the study and Merck for funding contribution to the trial. The authors express their gratitude to the investigators, site staff, the Oncodistinct network for their support, and the CTSU department from the Jules Bordet Institute for the assistance in clinical trial running and the previous fellows. We are grateful to the BCTL team of the Jules Bordet Institute for the central bio-banking of biological samples and for conducting translational analysis. We also thank the IMDC committee who reviewed the interim analysis. This work is an investigator-initiated, institution-sponsored study, with the Jules Bordet Institute, an academic hospital affiliated with the Free University of Brussels (Universit\u00E9 Libre de Bruxelles), Brussels, Belgium, serving as the sponsor. Funding to conduct the trial and drug (avelumab) supply were provided by the healthcare business of Merck KGaA, Darmstadt, Germany (no grant number), which had no role in study design, data collection, data analysis, data interpretation or report writing.
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