Status:
Open
Clinicaltrials.gov identifier:
Sponsor:
University Hospital, Rouen
Enrollment:
500
Study Design:
The GETUG/AFU V05 VESPER Phase III Trial randomized trial was conducted at 28 French centers comparing 4 cycles of gemcitabine and cisplatin (GC) to 6 cycles of dose dense or high-dose MVAC in the perioperative treatment of muscle-invasive bladder cancer (MIBC). Treatment was given either in the neoadjuvant or adjuvant window. Patients with pure or mixed urothelial bladder cancer were enrolled but neuroendocrine histology was excluded. All patients were platinum-eligible.
Rationale:
Gemcitabine and cisplatin are commonly used for perioperative (neoadjuvant or adjuvant) chemotherapy based on data demonstrating similar efficacy with better tolerance as compared to MVAC (methotrexate, vinblastine, doxorubicin, and cisplatin) in metastatic disease. In metastatic disease, high-dose (HD)-MVAC has better efficacy and this trial evaluates whether HD-MVAC has better efficacy in the perioperative setting in terms of progression-free survival.
Endpoints:
The primary endpoint was progression-free survival (PFS) at three years.
Comments:
The trial demonstrated a better organ-confined rate and a better PFS at 3 years in the HD-MVAC arm. Among the planned cycles in each arm of the trial, fewer patients in the HD-MVAC arm were treated with all planned cycles compared to the GC arm. Despite that, the cystectomy rate was the same in both arms suggesting that if a patient can tolerate this neoadjuvant regimen, it may result in better local control and progression-free survival. This regimen should be considered as a new standard for fit patients with muscle invasive urothelial cancer. The small number of patients treated with adjuvant chemotherapy prevent any conclusions about these regimens given on an adjuvant basis.
Results:
Overall, 437 patients (88%) received neoadjuvant chemotherapy: 84% of the patients in the GC arm and 60% of the patients in the HD-MVAC arm received all planned cycles. 90% and 91% of the patients underwent surgery respectively and organ-confined disease (<ypT3N0) was more frequently seen in the HD-MVAC arm (77% vs. 63%, p=0.001) respectively. The adjuvant group was smaller (only 54 patients) with 81% of the patients in the GC arm and 40% of the patients in the HD-MVAC arm receiving all planned cycles. Overall, the PFS at three years was better in the HD-MVAC arm (64% vs. 56%, HR = 0.77 (95% CI, 0.57-1.02), p=0.066) in all patients (neoadjuvant and adjuvant) but it was significantly better in the neoadjuvant group (66% vs. 56%, HR = 0.70 (95% CI, 0.51-0.96), p=0.025). OS data are not mature yet and final analysis will be done after a median follow-up of 5 years.
