The recent update of the phase III VESPER trial, a multicentre, randomized study, has shown that dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) provides superior overall survival (OS) at 5 years and significantly improves disease-specific survival (DSS) compared to gemcitabine and cisplatin (GC) in the perioperative setting for patients with muscle-invasive bladder cancer (MIBC).

In this trial, 500 eligible MIBC patients with cT2-cT4a N0 M0 for patients receiving NAC or pT3 or pT4 or pN+, M0 for patients receiving adjuvant chemotherapy; were randomly assigned to receive 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 majority of patients (88%) received neoadjuvant chemotherapy, and in the dd-MVAC arm, 60% received the planned 6 cycles, while 84% received 4 cycles in the GC arm.

The primary endpoint of the VESPER trial , previously reported, showed that dd-MVAC improved-3 years progression free survival (PFS) compared to GC. Additionally, In the neoadjuvant group, dd-MVAC arm demonstrated better bladder local control and a significant difference in 3-year PFS (p=0.025).

In the final analysis after median follow-up of 5 years, the secondary end point of OS at 5 years was improved in the dd-MVAC arm (64% vs 56%, HR=0.77, p=0.078), as well as disease-specific survival (DSS) (5-year rate: 72% vs 59%, HR=0.63, p=0.004). In the neoadjuvant group specifically, OS was significantly improved in the dd-MVAC arm (66% vs 57%, HR, 0.71, P=0.032) as was DSS (75% vs 60%, HR, 0.56, P=0.001).

Meanwhile, In the adjuvant group, the results were not conclusive due to the limited sample size (n=56).

Vesper represents a significant milestone in the history of chemotherapy for bladder cancer. It’s results confirm the undeniable superiority of dd-MVAC over GC as neoadjuvant chemotherapy and sets a new standard of care in the neoadjuvant settings.