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Expert Point of View: Enrique Grande, MD


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Enrique Grande, MD

Enrique Grande, MD

Invited discussant Enrique Grande, MD, of the Medical Oncology Department at MD Anderson Cancer Center Madrid, said that the VESPER trial should really be regarded as a neoadjuvant trial, since 88% of the patients enrolled were treated in the neoadjuvant setting. He focused the rest of his remarks on the neoadjuvant analysis.

“VESPER helps answer two important questions about the perioperative treatment of muscle-invasive bladder cancer,” Dr. Grande stated: “Is neoadjuvant therapy better than adjuvant? And is dd-MVAC [dose-dense methotrexate, vinblastine, doxorubicin, cisplatin] better than [gemcitabine plus cisplatin]?” The answer to both those questions is “yes.”

Other questions that remain to be answered include:

  • What is the optimal duration of treatment?
  • Does radiation play a role?
  • Are there any biomarkers?
  • Are there options for cisplatin-ineligible patients?
  • What is the role of immunotherapy and new targeted agents?

‘Potentially Practice-Changing’

“This trial is potentially practice-changing,” he stated. “Progression-free survival at 3 years may be more relevant than pathologic complete response, an endpoint we have used in other trials,” Dr. Grande said.

“Compared with historical data, the regimen of dd-MVAC performed quite well. It is also comparable with immunotherapy and [gemcitabine plus cisplatin],” he continued. “The issue is toxicity—just 60% of the dd-MVAC arm received the preplanned six cycles, and there was more nausea, vomiting, asthenia, and anemia with dd-MVAC, but that is the cost we have to pay,” he said.

Based on these results, he suggested that dd-MVAC should be the control arm in future neoadjuvant trials. 

DISCLOSURE: Dr. Grande reported receiving honoraria or serving as an advisor to Advanced Accelerator Applications, Amgen, Angelini, Astellas, AstraZeneca, Bayer, Blueprint, Bristol Myers Squibb, Caris Life Sciences, Celgene, Clovis Oncology, Eisai, Esteve, EUSA Pharma, Genetracer, GlaxoSmithKline, Guardant Health, HRA-Pharma, Ipsen, ITM, Janssen, Lexicon, Lilly, Merck KGaA, MSD, NanoString Technology, Natera, Novartis, OncoDNA (BioSequence), Pafex, PharmaMar, Pierre Fabre, Roche, Pfizer, Sanofi-Genzyme, Serview, Taiho, Thermo, and Fisher Scientific.


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The VESPER phase III trial answers some key questions regarding the optimal management of muscle-invasive bladder cancer. The study found that the neoadjuvant regimen of dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) was superior to standard gemcitabine/cisplatin in...

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