TY - JOUR
T1 - Dose-Dense Methotrexate, Vinblastine, Doxorubicin, and Cisplatin With or Without Panitumumab in Patients With Advanced Urothelial Carcinoma
T2 - Multicenter, Randomized, French Unicancer GETUG/AFU 19 Study
AU - Culine, Stéphane
AU - Fléchon, Aude
AU - Gravis, Gwenaelle
AU - Roubaud, Guilhem
AU - Loriot, Yohann
AU - Joly, Florence
AU - Barthélémy, Philippe
AU - Assaf, Elias
AU - Mahammedi, Hakim
AU - Beuzeboc, Philippe
AU - Houédé, Nadine
AU - Rolland, Frédéric
AU - Guillot, Aline
AU - Gross-Goupil, Marine
AU - Spano, Jean Philippe
AU - Tartas, Sophie
AU - Deblock, Mathilde
AU - Chevreau, Christine
AU - Serrate, Camille
AU - Manduzio, Hélène
AU - Habibian, Muriel
AU - Thézénas, Simon
AU - Allory, Yves
N1 - Publisher Copyright:
© 2021
PY - 2021/8/1
Y1 - 2021/8/1
N2 - 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.
AB - 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.
KW - Chemotherapy
KW - Cisplatin
KW - Epidermal growth factor receptor
KW - Monoclonal antibody
KW - Transitional cell carcinoma
UR - http://www.scopus.com/inward/record.url?scp=85102997416&partnerID=8YFLogxK
U2 - 10.1016/j.clgc.2021.02.005
DO - 10.1016/j.clgc.2021.02.005
M3 - Article
C2 - 33753043
AN - SCOPUS:85102997416
SN - 1558-7673
VL - 19
SP - e216-e222
JO - Clinical Genitourinary Cancer
JF - Clinical Genitourinary Cancer
IS - 4
ER -