Informace o publikaci

Cediranib With mFOLFOX6 Versus Bevacizumab With mFOLFOX6 As First-Line Treatment for Patients With Advanced Colorectal Cancer: A Double-Blind, Randomized Phase III Study (HORIZON III)

Autoři	SCHMOLL Hans-Joachim CUNNINGHAM David SOBRERO Alberto KARAPETIS Christos S. ROUGIER Philippe KOSKI Sheryl L. KOCÁKOVÁ Ilona BONDARENKO Igor BODOKY Gyoergy MAINWARING Paul SALAZAR Ramon BARKER Peter MOOKERJEE Bijoyesh ROBERTSON Jane VAN CUTSEM Eric
Rok publikování	2012
Druh	Článek v odborném periodiku
Časopis / Zdroj	Journal of clinical oncology
Fakulta / Pracoviště MU	Lékařská fakulta
Citace
Doi	http://dx.doi.org/10.1200/JCO.2012.42.5355
Obor	Onkologie a hematologie
Klíčová slova	TYROSINE KINASE INHIBITOR; OXALIPLATIN-BASED CHEMOTHERAPY; CLINICAL-TRIALS GROUP; CELL LUNG-CANCER; HIGHLY POTENT; PATIENTS PTS; COMBINATION; AZD2171; PLACEBO; MCRC
Popis	Purpose To compare the efficacy of cediranib (a vascular endothelial growth factor receptor tyrosine kinase inhibitor [VEGFR TKI]) with that of bevacizumab (anti-VEGF-A monoclonal antibody) in combination with chemotherapy as first-line treatment for advanced metastatic colorectal cancer (mCRC). Patients and Methods HORIZON III [Cediranib Plus FOLFOX6 Versus Bevacizumab Plus FOLFOX6 in Patients With Untreated Metastatic Colorectal Cancer] had an adaptive phase II/III design. Patients randomly assigned 1:1:1 received mFOLFOX6 [oxaliplatin 85 mg/m(2) and leucovorin 400 mg/m(2) intravenously followed by fluorouracil 400 mg/m(2) intravenously on day 1 and then continuous infusion of 2,400 mg/m(2) over the next 46 hours every 2 weeks] with cediranib (20 or 30 mg per day) or bevacizumab (5 mg/kg every 14 days). An independent end-of-phase II analysis concluded that mFOLFOX6/cediranib 20 mg met predefined criteria for continuation; subsequent patients received mFOLFOX6/cediranib 20 mg or mFOLFOX6/bevacizumab (randomly assigned 1:1). The primary objective was to compare progression-free survival (PFS). Conclusion Cediranib activity, in terms of PFS and OS, was comparable to that of bevacizumab when added to mFOLFOX6; however, the predefined boundary for PFS noninferiority was not met. The cediranib safety profile was consistent with previous studies but led to less favorable PROs compared with bevacizumab. Investigation of oral TKIs in CRC continues. J Clin Oncol 30: 3588-3595.