(UroToday.com) In the Proffered Paper session of the European Society for Medical Oncology (ESMO) Annual Congress focusing on non-prostate cancer genitourinary tumors, Dr. Pfister presented results of the GETUG/AFU VESPER V05 phase III trial assessing dose dense Methotrexate, Vinblastine, Doxorubicin and Cisplatin (dd-MVAC) compared to Gemcitabine and Cisplatin (GC) as perioperative chemotherapy for patients with muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (NCT 01812369).
This trial enrolled patients with pure or mixed urothelial bladder cancer who were cisplatin-eligible and had ECOG performance status 0-2. Based on staging imaging and TURBT, patients had to have at least cT2 disease without evidence of nodal involvement or distant metastasis (to be included in the neoadjuvant group) or >pT2 or pN+ non-metastatic disease (to be included in the adjuvant group).
Between February 2013 and February 2018, a total of 500 patients were randomized across 28 centers in France. Patients received either 4 cycles of GC every 3 weeks or 6 cycles of dd-MVAC every 2 weeks before surgery (neoadjuvant group) or after surgery (adjuvant group). The trial primarily assessed progression-free survival (PFS) at 3 years
Among the 500 patients included, 437 patients (88%) received neoadjuvant chemotherapy. Compared to their planned treatment courses, 60% of patients received the planned 6 cycles in the dd-MVAC arm and 84% received 4 cycles in the GC arm. Following chemotherapy 91% and 90% of patients underwent surgery in the dd-MVAC and GC arms, respectively. In terms of pathologic response, evidence of organ-confined disease following neoadjuvant chemotherapy (< ypT3N0) was observed more frequently among patients who received neoadjuvant dd-MVAC compared to those who received GS (77% vs 63%, p=0.001). In the adjuvant group, 40% of patients received 6 cycles in the dd-MVAC arm while 81% received 4 cycles in the GC arm.
Considering the entirety of the perioperative setting of the VESPER trial, three-year progression free survival was improved for patients in the dd-MVAC arm compared to those receiving GC (64% vs 56%, HR=0.77 (95% CI, 0.57-1.02), p=0.066). Additionally, time to progression (TTP) was improved, and this met statistical significance (3-year rate: 69% vs 58%, HR=0.68 (95% CI, 0.50-0.93), p=0.014).
Considering the two treatment approaches separately, in the neoadjuvant group, three-year progression free survival was significantly higher for the dd-MVAC arm than the GC arm (66% vs 56%, HR=0.70 (95% CI, 0.51-0.96), p=0.025). However, in the adjuvant group, results were inconclusive due to the limited number of patients included (n=56).
Additionally, assessing overall survival, in the overall study cohort, this just failed to meet statistical significance (HR 0.74, 95% CI 0.55-1.00) while among those receiving neoadjuvant chemotherapy, dd-MVAC significantly improved overall survival (HR 0.66, 95% CI 0.47-0.92).
Dr. Pfister therefore concluded that, based on the data from the VESPER phase III trial, perioperative ddMVAC is associated with a three-year progression-free survival benefit compared to GC. Further, among those receiving neoadjuvant chemotherapy, improved bladder tumor local control was noted. Dr. Pfister therefore suggested that dd-MVAC should now become the gold standard for neoadjuvant chemotherapy.
Presented by: Christian Pfister, MD, PhD, Department of Urology, Charles Nicolle University Hospital