For the first time since 20 years in the bladder peri-operative setting, the authors have design a randomised phase III controlled study comparing the efficacy of GC or dd-MVAC in patients for whom chemotherapy has been decided before or after surgery. The results of the GETUG/AFU VESPER V05, were reported by Prof. Christian Pfister from the Urology Department, Hopital Charles-Nicolle - CHU de Rouen in Rouen, France on behalf of the VESPER V05 study team during the proffered papers session on genitourinary cancers, non-prostate at ESMO Congress 2021 (16-21 September).
Prof. Pfister explained to the audience that the optimal perioperative chemotherapy regimen for patients with muscle invasive bladder cancer (MIBC) is not really defined today. Between February 2013 and February 2018, the study team randomised 500 patients in 28 French cancer centres to receive either 4 cycles of gemcitabine and cisplatin (GC) every 3 weeks or 6 cycles of dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) every 2 weeks before surgery in the neoadjuvant group or after surgery in the adjuvant group. The study primary endpoint was the progression-free survival (PFS) at 3 years.
In total, 437 patients (88%) received neoadjuvant chemotherapy; of those, 60% of patients received the planned 6 cycles in the dd-MVAC arm and 84% received 4 cycles in the GC arm. Subsequently, 91% and 90% of patients underwent surgery. Organ-confined response, defined as < ypT3N0, was observed more frequently in the dd-MVAC arm, 77% versus 63% (p = 0.001). In the adjuvant group, 40% of patients received 6 cycles in the dd-MVAC arm and 81% received 4 cycles in the GC arm. In the perioperative setting of this study, the PFS at 3 years was improved in the dd-MVAC arm, 64% versus 56% (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.57 1.02; p = 0.066). Time to progression (TTP) was also improved in the dd-MVAC arm with TTP 3-year rate of 69% versus 58% (HR 0.68, 95% CI 0.50 0.93; p = 0.014). In the neoadjuvant group, the PFS at 3 years was significantly higher for the dd-MVAC arm, 66% versus 56% (HR 0.70, 95% CI 0.51 0.96; p = 0.025). In the adjuvant group, the results were not conclusive due to the limited sample size.
In this academic phase III study, the authors reported a benefit in PFS at 3 years in the dd-MVAC arm. In the neoadjuvant group, a better bladder tumour local control with a significant improvement in PFS at 3 years were observed suggesting that dd-MVAC regimen should now become the gold standard for neoadjuvant chemotherapy in MIBC.
This study was funded by a grant from the French Ministry of Health.
652O – Pfister C, Gravis G, Flechon A, et al. Dose-dense methotrexate, vinblastine, doxorubicin and cisplatin (dd-MVAC) or gemcitabine and cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC): Results of the GETUG/AFU VESPER V05 phase III trial. ESMO Congress 2021 (16-21 September).