The optimal perioperative chemotherapy regimen for patients with nonmetastatic muscle-invasive bladder cancer is not defined.
Between February 2013 and March 2018, 500 patients were randomly assigned in 28 French centers and received either six cycles of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) once every 2 weeks or four cycles of gemcitabine and cisplatin (GC) once every 3 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). We report the primary end point of the GETUG-AFU V05 VESPER trial (ClinicalTrials.gov identifier: NCT01812369): progression-free survival (PFS) at 3 years. Secondary end points were time to progression and overall survival.
Four hundred thirty-seven patients (88%) received neoadjuvant chemotherapy; 60% of patients received the planned six cycles in the dd-MVAC arm, 84% received four cycles in the GC arm, and thereafter, 91% and 90% of patients underwent surgery, respectively. Organ-confined response (< ypT3N0) was observed more frequently in the dd-MVAC arm (77% v 63%, P = .001). In the adjuvant group, 40% of patients received six cycles in the dd-MVAC arm, and 81% of patients received four cycles in the GC arm. For all patients in the clinical trial, 3-year PFS was improved in the dd-MVAC arm, but the study did not meet its primary end point (3-year rate: 64% v 56%, hazard ratio [HR] = 0.77 [95% CI, 0.57 to 1.02], P = .066); nevertheless, the dd-MVAC arm was associated with a significantly longer time to progression (3-year rate: 69% v 58%, HR = 0.68 [95% CI, 0.50 to 0.93], P = .014). In the neoadjuvant group, PFS at 3 years was significantly higher in the dd-MVAC arm (66% v 56%, HR = 0.70 [95% CI, 0.51 to 0.96], P = .025).
In the VESPER trial, dd-MVAC improved 3-years PFS over GC. In the neoadjuvant group, a better bladder tumor local control and a significant improvement in 3-year PFS were observed in the dd-MVAC arm.
Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2022 Mar 07 [Epub ahead of print]
Christian Pfister, Gwenaelle Gravis, Aude Fléchon, Christine Chevreau, Hakim Mahammedi, Brigitte Laguerre, Aline Guillot, Florence Joly, Michel Soulié, Yves Allory, Valentin Harter, Stéphane Culine, VESPER Trial Investigators
Department of Urology, Charles Nicolle University Hospital, Rouen, France., Department of Medical Oncology, Paoli-Calmette Institute, Marseille, France., Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France., Department of Medical Oncology, ICR-IUCT Oncopole, Toulouse, France., Department of Medical Oncology, Jean Perrin Cancer Center, Clermont-Ferrand, France., Department of Medical Oncology, Eugène Marquis Cancer Center, Rennes, France., Department of Medical Oncology, Lucien Neuwirth Cancer Institute, St Priest, France., Department of Medical Oncology, Baclesse Cancer Center, Caen, France., Department of Urology, Rangueil University Hospital, Toulouse, France., Department of Pathology, Curie Institute, Saint-Cloud, France., North-West Canceropole Data Center, Baclesse Cancer Center, Caen, France., Department of Medical Oncology, Saint-Louis Hospital, AP-HP, Faculté de Paris, France.