title: Axitinib and/or bevacizumab with modified FOLFOX-6 as first-line therapy for metastatic colorectal cancer: a randomized phase 2 study.
abstract: 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).
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Sarah Cannon Research Institute/Tennessee Oncology, PLLC, Nashville, Tennessee, USA. jinfante@tnonc.com
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Infante
authors.forename: Tony R
authors.initials: TR
authors.lastname: Reid
authors.forename: Allen L
authors.initials: AL
authors.lastname: Cohn
authors.forename: William J
authors.initials: WJ
authors.lastname: Edenfield
authors.forename: Terrence P
authors.initials: TP
authors.lastname: Cescon
authors.forename: John T
authors.initials: JT
authors.lastname: Hamm
authors.forename: Imtiaz A
authors.initials: IA
authors.lastname: Malik
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Rado
authors.forename: Philip J
authors.initials: PJ
authors.lastname: McGee
authors.forename: Donald A
authors.initials: DA
authors.lastname: Richards
authors.forename: Jamal
authors.initials: J
authors.lastname: Tarazi
authors.forename: Brad
authors.initials: B
authors.lastname: Rosbrook
authors.forename: Sinil
authors.initials: S
authors.lastname: Kim
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Cartwright
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077784:Axitinib; D000068258:Bevacizumab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage / Q000009:adverse effects; D007191:Indazoles / Q000008:administration & dosage / Q000009:adverse effects; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007093:Imidazoles; D007191:Indazoles; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000077784:Axitinib; D002955:Leucovorin; D005472:Fluorouracil
keywords: FOLFOX; axitinib; bevacizumab; colorectal cancer