medwireNews: Neoadjuvant dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) may delay disease progression or death versus gemcitabine plus cisplatin in people with nonmetastatic muscle-invasive bladder cancer (MIBC), research suggests.
Christian Pfister (Charles Nicolle Rouen University Hospital, France) and co-investigators believe their phase 3 trial “is a milestone in the history of chemotherapy for MIBC,” because there is currently no well-defined optimal perioperative chemotherapy regimen for these patients and “[l]evel I evidence in international guidelines was established with regimens that are no longer currently used.”
The VESPER trial included 493 patients who were randomly assigned to receive either six cycles of dd-MVAC once every 2 weeks (n=248) or four cycles of gemcitabine plus cisplatin once every 3 weeks (n=245).
Of these, 88% were treated in the neoadjuvant setting and the remainder received the drugs as adjuvant therapy.
Overall, the 3-year progression-free survival (PFS) was 64% in the dd-MVAC arm and 56% in the gemcitabine plus cisplatin arm, a nonsignificant difference that meant the trial did not meet its primary endpoint.
However, the researchers note that there was a significant interaction between treatment arm and when the perioperative chemotherapy was given.
Specifically, there was a significant 30% lower risk for disease progression or death among patients who received neoadjuvant dd-MVAC relative to those who received neoadjuvant gemcitabine plus cisplatin, with 3-year PFS rates of 66% and 56%, respectively. By contrast, “the result on multivariate model was not conclusive” when the treatments were given in the adjuvant setting, says the team.
For the secondary outcome of time to progression, Pfister and team observed a significant 32% lower risk for progression within 3 years among the people who received dd-MVAC at any time perioperatively versus those who received gemcitabine plus cisplatin (69 vs 58%), and a significant 38% lower risk when assessing only patients given dd-MVAC or gemcitabine plus cisplatin in the neoadjuvant setting (71 vs 59%).
The investigators note that the majority of grade 3 or worse adverse events were hematologic in both groups, occurring in 52% of participants who received dd-MVAC and 55% of those given gemcitabine plus cisplatin.
Writing in the Journal of Clinical Oncology, Pfister et al conclude: “Our prospective randomized phase III study suggests that in the future, dd-MVAC regimen should become the gold standard for neoadjuvant chemotherapy because of a higher local control rate and a significant improvement in 3-year PFS.”
They add that although overall survival data are not yet mature, they expect their findings “to confirm these results.”
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