ESMO 2021: GETUG/AFU VESPER V05 Phase III Trial of Dose Dense Methotrexate, Vinblastine, Doxorubicin and Cisplatin or Gemcitabine and Cisplatin As Perioperative Chemotherapy for Patients With MIBC

(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).

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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).

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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).

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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

Written by: Christopher J.D. Wallis, University of Toronto, Twitter: @WallisCJD during the 2021 European Society for Medical Oncology (ESMO) Annual Congress 2021, Thursday, Sep 16, 2021 – Tuesday, Sep 21, 2021.

 

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