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Axitinib and/or bevacizumab with modified FOLFOX‐6 as first‐line therapy for metastatic colorectal cancer: A randomized phase 2 study
Author(s) -
Infante Jeffrey R.,
Reid Tony R.,
Cohn Allen L.,
Edenfield William J.,
Cescon Terrence P.,
Hamm John T.,
Malik Imtiaz A.,
Rado Thomas A.,
McGee Philip J.,
Richards Donald A.,
Tarazi Jamal,
Rosbrook Brad,
Kim Sinil,
Cartwright Thomas H.
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28112
Subject(s) - medicine , bevacizumab , axitinib , folfox , oxaliplatin , clinical endpoint , colorectal cancer , phases of clinical research , oncology , surgery , gastroenterology , randomized controlled trial , chemotherapy , cancer , sunitinib
BACKGROUND In this multicenter, open‐label, randomized phase 2 trial, the authors evaluated the vascular endothelial growth factor receptor inhibitor axitinib, bevacizumab, or both in combination with chemotherapy as first‐line treatment of metastatic colorectal cancer (mCRC). METHODS Patients with previously untreated mCRC were randomized 1:1:1 to receive continuous axitinib 5 mg twice daily, bevacizumab 5 mg/kg every 2 weeks, or axitinib 5 mg twice daily plus bevacizumab 2 mg/kg every 2 weeks, each in combination with modified 5‐fluorouracil/leucovorin/oxaliplatin (FOLFOX‐6). The primary endpoint was the objective response rate (ORR). RESULTS In all, 126 patients were enrolled from August 2007 to September 2008. The ORR was numerically inferior in the axitinib arm (n = 42) versus the bevacizumab arm (n = 43; 28.6% vs 48.8%; 1‐sided P = .97). Progression‐free survival (PFS) (11.0 months vs 15.9 months; 1‐sided P = .57) and overall survival (OS) (18.1 months vs 21.6 months; 1‐sided P = .69) also were numerically inferior in the axitinib arm. Similarly, efficacy endpoints for the axitinib/bevacizumab arm (n = 41) were numerically inferior (ORR, 39%; PFS, 12.5 months; OS, 19.7 months). The patients who received axitinib had fewer treatment cycles compared with other arms. Common all‐grade adverse events across all 3 treatment arms were fatigue, diarrhea, and nausea (all ≥49%). Hypertension and headache were more frequent in the patients who received axitinib. Patients in the bevacizumab arm had the longest treatment exposures and the highest rates of peripheral neuropathy. CONCLUSIONS Neither the addition of continuous axitinib nor the axitinib/bevacizumab combination to FOLFOX‐6 improved ORR, PFS, or OS compared with bevacizumab as first‐line treatment of mCRC. Cancer 2013;119:2555–2563 . © 2013 American Cancer Society .