Perioperative Dose-Dense MVAC vs Gemcitabine/Cisplatin in Nonmetastatic Muscle-Invasive Bladder Cancer

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As reported in the Journal of Clinical Oncology by Pfister et al, the French phase III GETUG-AFU V05 VESPER trial showed a nonsignificant improvement in 3-year progression-free survival with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd- MVAC) vs gemcitabine/cisplatin given as neoadjuvant or adjuvant therapy in patients with nonmetastatic muscle-invasive bladder cancer. Neoadjuvant MVAC significantly improved 3-year progression-free survival, and MVAC was associated with delayed time to disease progression among all patients.

In the multicenter trial, 493 evaluable patients with planned cystectomy were randomly assigned between February 2013 and March 2018 to receive six cycles of dd-MVAC once every 2 weeks (n = 248) or four cycles of gemcitabine/cisplatin once every 3 weeks (n = 245) as neoadjuvant treatment (88% of patients; n = 218 vs 219) or adjuvant therapy (n = 30 vs 26). The primary endpoint was 3-year progression-free survival.

Progression-Free Survival

Among patients receiving neoadjuvant therapy, 60% of patients received the planned six cycles in the dd-MVAC group and 84% received four cycles in the gemcitabine/cisplatin arm; 91% and 90% of patients underwent surgery, respectively. Complete pathologic response (ypT0pN0) was observed in 42% vs 36% of patients (P = .2). Organ-confined response (< ypT3N0) was observed in 77% vs 63% of patients (P = .001). Among patients receiving adjuvant therapy, 40% received six cycles of dd-MVAC and 81% received four cycles of gemcitabine/cisplatin.


  • Among all patients, 3-year progression-free survival was 64% in the dd-MVAC group vs 56% in the gemcitabine/cisplatin group.
  • In the neoadjuvant group (88% of population), 3-year progression-free survival was 66% vs 56%.

Among all patients, 3-year progression-free survival was 64% in the dd-MVAC group vs 56% in the gemcitabine/cisplatin group (hazard ratio [HR] = 0.77, 95% confidence interval [CI] = 0.57–1.02, P = .066). In the neoadjuvant treatment group, 3-year progression-free survival was 66% vs 56% (HR = 0.70, 95% CI = 0.51–0.96, P = .025). Among all patients, progression-free rates at 3 years were 69% vs 58% (HR = 0.68, 95% CI = 0.50–0.93, P = .014), including rates of 71% vs 59% (HR = 0.62, 95% CI = 0.44–0.85, P = .005) in the neoadjuvant group.

Overall survival will be analyzed at 5 years of follow-up. Current estimated hazard ratios for the dd-MVAC group vs gemcitabine/cisplatin group after 40 months are 0.74 (95% CI = 0.55­–1.00) among all patients and 0.66 (95% CI = 0.47–0.92) in the neoadjuvant group.

Adverse Events

The most common grade ≥ 3 toxicities were hematologic (occurring in 52% of the dd-MVAC group vs 55% in the gemcitabine/cisplatin group) with grade ≥ 3 anemia being more common in the dd-MVAC group (P < .001). Grade ≥ 3 asthenia was reported in 14% vs 4.1% of patients (P < .001). Grade ≥ 3 gastrointestinal toxicity was more common in the dd-MVAC group (P = .003). Four patients died during study chemotherapy, including three in the dd-MVAC group (due to sudden death, pulmonary embolism, and septic shock).

The investigators concluded, “In the VESPER trial, dd-MVAC improved 3-year progression-free survival over gemcitabine/cisplatin. In the neoadjuvant group, a better bladder tumor local control and a significant improvement in 3-year progression-free survival were observed in the dd-MVAC arm.”

Christian Pfister, MD, PhD, of the Urology Department, Charles Nicolle Rouen University Hospital, Rouen, is the corresponding author for the Journal of Clinical Oncology article.  

Disclosure: The study was supported by the French Ministry of Health. For full disclosures of the study authors, visit

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