2. UroToday Home
  3. Recent Abstracts
  4. Urologic Oncology
  5. Bladder Cancer

Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With or Without Panitumumab in Patients With Advanced Urothelial Carcinoma: Multicenter, Randomized, French Unicancer GETUG/AFU 19 Study

This study looked at whether epidermal growth factor receptor inhibition by the monoclonal antibody panitumumab could increase the efficacy of standard chemotherapy in advanced urothelial cancer. Results were disappointing, with higher toxicity and no improvement in efficacy in the combination arm.


Background: Epidermal growth factor receptor (EGFR) overexpression is frequent and associated with poor outcome in urothelial carcinoma. EGFR inhibition could improve the antitumor activity of chemotherapy.

Patients and methods: Patients with advanced, treatment-naïve, histologically confirmed advanced urothelial carcinoma and no HRAS or KRAS mutation in the primary tumor received dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (dd-MVAC) without or with the anti-EGFR monoclonal antibody panitumumab (Pmab). A randomized (1:2) phase II design was used with progression-free survival (PFS) as the primary endpoint.

Results: Ninety-seven eligible patients were randomized; 96 patients were evaluable for toxicity and 87 for efficacy. The median PFS were 6.8 months (95% confidence interval [CI], 6.3-9.2) for dd-MVAC and 5.7 months (95% CI, 4.6-6.4 months) for dd-MVAC+Pmab. For both immunohistochemical and molecular definition of basal/squamous-like (BASQ) tumors, no difference was observed in objective response rates or PFS between the two arms in BASQ and non-BASQ tumors.

Conclusion: dd-MVAC+Pmab was associated with more serious adverse events and no improvement in efficacy outcomes.

Stéphane Culine 1, Aude Fléchon 2, Gwenaelle Gravis 3, Guilhem Roubaud 4, Yohann Loriot 5, Florence Joly 6, Philippe Barthélémy 7, Elias Assaf 8, Hakim Mahammedi 9, Philippe Beuzeboc 10, Nadine Houédé 11, Frédéric Rolland 12, Aline Guillot 13, Marine Gross-Goupil 14, Jean-Philippe Spano 15, Sophie Tartas 16, Mathilde Deblock 17, Christine Chevreau 18, Camille Serrate 19, Hélène Manduzio 20, Muriel Habibian 20, Simon Thézénas 21, Yves Allory 22


  1. Department of Medical Oncology Saint-Louis University Hospital, AP-HP, Paris, France. 
  2. Department of Medical Oncology, Léon Bérard Cancer Center, Lyon, France.
  3. Department of Medical Oncology, Paoli Calmettes Institute, Marseille, France.
  4. Department of Medical Oncology, Bergonié Institute, Bordeaux, France.
  5. Department of Cancer Medicine, Gustave Roussy, Inserm U981, Villejuif, France.
  6. Department of Medical Oncology, François Baclesse Cancer Center, Caen, France.
  7. Department of Medical Oncology, University Hospital, Strasbourg, France.
  8. Department of Medical Oncology, Henri Mondor University Hospital, AP-HP, Créteil, France.
  9. Department of Medical Oncology, Jean Perrin Cancer Center, Clermont-Ferrand, France.
  10. Department of Medical Oncology, Curie Institute, Paris, France.
  11. Gard Cancer Institute, University Hospital, Nîmes, Inserm U1194, Montpellier Cancer Institute, University of Montpellier, Montpellier, France.
  12. Department of Medical Oncology, René Gauducheau Cancer Center, Nantes, France.
  13. Department of Medical Oncology, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France.
  14. Department of Medical Oncology, University Hospital, Bordeaux, France.
  15. Department of Medical Oncology, Pitié-Salpétrière University Hospital, AP-HP, Paris, France.
  16. Department of Medical Oncology, Lyon-Sud University Hospital, Lyon, France.
  17. Department of Medical Oncology, Alexis Vautrin Cancer Center, Nancy, France.
  18. Department of Medical Oncology, ICR-IUCT Oncopole, Toulouse, France.
  19. Department of Medical Oncology, Diaconesses Croix Saint-Simon Hospital, Paris, France.
  20. Unicancer, Paris, France.
  21. Department of Biostatistics, Montpellier Cancer Institute, Montpellier, France.
  22. Department of Pathology, René Huguenin Curie Institute, Saint Cloud, France.

Source: Culine S., Fléchon A., Gravis G. et al. "Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With or Without Panitumumab in Patients With Advanced Urothelial Carcinoma: Multicenter, Randomized, French Unicancer GETUG/AFU 19 Study." Clinical Genitourinary Cancer, Vol. 19, No. 4, e216–e222.

Read an Expert Commentary by Bishoy Faltas, MD