As reported in The Lancet Oncology by Pfister et al, a 5-year analysis of the French phase III VESPER trial showed no improvement in overall survival with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) vs gemcitabine and cisplatin (GC) in the total perioperative (intention-to-treat [ITT]) population of patients with muscle-invasive bladder cancer. Improvement in overall survival with dd-MVAC was observed among patients treated in the neoadjuvant setting, who constituted the majority of the study population.
The primary analysis of the trial showed a 3-year progression-free survival benefit with dd-MVAC vs GC given in the neoadjuvant setting but not in the total population.
Study Details
In the multicenter trial, 493 eligible patients (ITT population) were randomly assigned between February 2013 and March 2018 to receive dd-MVAC every 2 weeks for a total of six cycles (n = 248) or GC every 3 weeks for a total of four cycles (n = 245) in either the neoadjuvant or adjuvant setting. A total of 89% of patients received treatment in the neoadjuvant setting, including 218 in the dd-MVAC group and 219 in the GC group; a total of 11% received study regimens in the adjuvant setting.
Key Findings
In the total ITT population, the overall survival rate at 5 years was 64% (95% confidence interval [CI] = 58%–70%) in the dd-MVAC group vs 56% (95% CI = 50%–63%) in the GC group (stratified hazard ratio [HR] = 0.79, 95% CI = 0.59–1.05). Cumulative incidence of death from bladder cancer at 5 years was 27% (95% CI = 21%–32%) in the dd-MVAC group vs 40% (95% CI = 34%–46%) in the GC group (stratified HR = 0.61, 95% CI = 0.45–0.84).
Among patients receiving study treatment in the neoadjuvant setting, the 5-year overall survival rate was 66% (95% CI = 60%–73%) in the dd-MVAC group vs 57% (95% CI = 50%–64%) in the GC group (HR = 0.71, 95% CI = 0.52–0.97). Cumulative incidence of death from bladder cancer at 5 years was 24% (95% CI = 18%–30%) in the dd-MVAC group vs 38% (95% CI = 32%–45%) in the GC group (HR = 0.55, 95% CI = 0.39–0.78).
Results in patients receiving study treatment in the adjuvant setting were inconclusive because of the small sample size.
Bladder cancer progression was the cause of 157 of the total 190 deaths (83%); other causes of death included cardiovascular events (4%), death related to chemotherapy toxicity (2%), and secondary cancers (2%).
The investigators concluded: “Our results on overall survival at 5 years were in accordance with the primary endpoint analysis (3-year progression-free survival). We found no evidence of improved overall survival with dd-MVAC over GC in the perioperative setting, but the data support the use of six cycles of dd-MVAC over four cycles of GC in the neoadjuvant setting. These results should impact practice and future trials of immunotherapy in bladder cancer.”
Christian Pfister, MD, PhD, of the Department of Urology, Charles Nicolle University Hospital, Rouen, is the corresponding author of The Lancet Oncology article.
Disclosure: The study was funded by the French National Cancer Institute. For full disclosures of the study authors, visit thelancet.com.
