The VESPER trial, a phase 3 study evaluating perioperative chemotherapy regimens for muscle-invasive bladder cancer, has reported its 5-year overall survival (OS) and time to death due to bladder cancer endpoints. While the study did not find a statistically significant OS benefit for dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) compared to gemcitabine and cisplatin (GC) in the overall perioperative setting, a notable improvement was observed in the neoadjuvant subgroup.
The open-label, randomized trial, conducted across 28 centers in France, enrolled 500 patients with primary muscle-invasive urothelial carcinoma. Patients were randomized to receive either dd-MVAC (every 2 weeks for six cycles) or GC (every 3 weeks for four cycles). The primary endpoint, 3-year progression-free survival, was previously reported, showing an advantage for dd-MVAC in the neoadjuvant setting but not overall. This report focuses on the secondary endpoints of OS and time to death due to bladder cancer at the 5-year mark.
Key Findings at 5 Years
After a median follow-up of 5.3 years, 190 deaths were reported. In the intention-to-treat (ITT) population, 5-year OS was 64% with dd-MVAC and 56% with GC (HRstrat 0.79, 95% CI 0.59-1.05). Time to death due to bladder cancer favored dd-MVAC, with a 5-year cumulative incidence of death of 27% versus 40% for GC (HRstrat 0.61, 95% CI 0.45-0.84).
Neoadjuvant Subgroup Analysis
In the neoadjuvant subgroup, comprising 89% of the patients, dd-MVAC demonstrated a significant improvement in 5-year OS (66% vs 57%; HR 0.71, 95% CI 0.52-0.97) and time to death due to bladder cancer (5-year cumulative incidence: 24% vs 38%; HR 0.55, 95% CI 0.39-0.78).
Implications for Clinical Practice
The results suggest that six cycles of dd-MVAC should be considered over four cycles of GC in the neoadjuvant setting for muscle-invasive bladder cancer. These findings are particularly relevant given that bladder cancer progression accounted for 83% of the deaths in the study. The authors suggest that these results should inform practice and future trials of immunotherapy in bladder cancer.
Study Limitations
The study is limited by its open-label design. The adjuvant subgroup analysis was inconclusive due to the small sample size. Further research is warranted to explore the optimal chemotherapy regimen in the adjuvant setting.
