No Survival Benefit With Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin for Patients With Muscle-Invasive Bladder Cancer

5-Year Results From the VESPER Trial

According to 5-year survival data from the phase 3 VESPER trial, there was no evidence of improved overall survival with dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) among patients with muscle-invasive bladder cancer, when compared with gemcitabine and cisplatin. However, in the neoadjuvant setting, dd-MVAC may be preferable to gemcitabine-cisplatin.

Christian Pfister, MD, PhD, Charles Nicolle University Hospital, Rouen, France, and coauthors wrote, “The optimal perioperative chemotherapy for patients with muscle-invasive bladder cancer is not defined.” Previous results from the VESPER trial reported the 3-year progression-free survival with dd-MVAC vs gemcitabine-cisplatin among patients who received neoadjuvant therapy, but not in the overall perioperative setting. These results represent the secondary end points of overall survival and time to death due to bladder cancer with 5 years of follow-up.

VESPER was an open-label phase 3 trial which randomized 493 patients with muscle-invasive urothelial carcinoma on a 1-to-1 basis to receive either dd-MVAC every 2 weeks for a total of 6 cycles (n = 248), or gemcitabine-cisplatin every 3 weeks for a total of 4 cycles (n = 245). The median follow-up was 5 years, 3 months. In the total intention-to-treat population, there was no evidence of an association of overall survival at 5 years with dd-MVAC vs gemcitabine-cisplatin. The time to death due to bladder cancer was increased in the dd-MVAC group when compared to the gemcitabine-cisplatin group. Among the subgroup of patients who received neoadjuvant chemotherapy, both the overall survival at 5 years and the time to death due to cancer were improved in the dd-MVAC group vs the gemcitabine-cisplatin group. In the adjuvant chemotherapy subgroup, results were inconclusive due to small sample size.

Dr Pfister et al concluded, “Our results on overall survival at 5 years were in accordance with the primary endpoint analysis (3-year progression-free survival).” While there was no benefit to overall survival from dd-MVAC vs gemcitabine-cisplatin in the perioperative setting, “the data support the use of [6] cycles of dd-MVAC over [4] cycles of [gemcitabine-cisplatin] in the neoadjuvant setting,” they added.

Source:

Pfister C, Gravis G, Flechon A, et al. Perioperative dose-dense methotrexate, vinblastine, doxotubicin, and cisplatin in muscle-invasive bladder cancer (VESPER): survival endpoints at 5 years in an open-label, randomised, phase 3 study. Lancet Oncol. Published online December 21, 2023. doi: 10.1016/S1470-2045(23)00587-9