title: Axitinib or bevacizumab plus FOLFIRI or modified FOLFOX-6 after failure of first-line therapy for metastatic colorectal cancer: a randomized phase II study.
abstract: OBJECTIVE
  Axitinib, a potent and selective second-generation inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, shows activity in multiple tumor types, including those refractory to previous antiangiogenic therapy. This randomized, multicenter, parallel-group, open-label phase II trial compared axitinib with bevacizumab each in combination with 5-fluorouracil/leucovorin/oxaliplatin (FOLFOX) or 5-fluorouracil/leucovorin/irinotecan (FOLFIRI) for second-line treatment of metastatic colorectal cancer.
  
  
  METHODS
  Patients were randomized 1:1 to axitinib 5 mg twice daily or bevacizumab 5 mg/kg every 2 weeks plus modified FOLFOX-6 (if previously treated with irinotecan) or FOLFIRI (if previously treated with oxaliplatin) and were stratified by performance status and prior bevacizumab therapy. Primary endpoint was progression-free survival.
  
  
  RESULTS
  In 171 patients, progression-free survival was 7.6 months with axitinib/FOLFOX vs. 6.4 months with bevacizumab/FOLFOX (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.55-1.96; 1-sided P = .55) and 5.7 months with axitinib/FOLFIRI vs. 6.9 months with bevacizumab/FOLFIRI (HR, 1.27; 95% CI, 0.77-2.11; 1-sided P = .83). Overall survival was 17.1 vs. 14.1 months with axitinib/FOLFOX and bevacizumab/FOLFOX (HR, 0.69; 95% CI, 0.37-1.27; 1-sided P = .12) and 12.9 vs. 15.7 months with axitinib/FOLFIRI and bevacizumab/FOLFIRI (HR, 1.36; 95% CI, 0.82-2.24; 1-sided P = .88). More grade ≥ 3 adverse events (eg, diarrhea, fatigue, decreased appetite) and treatment discontinuations due to adverse events occurred with axitinib.
  
  
  CONCLUSIONS
  Compared with bevacizumab, axitinib did not improve outcomes when added to second-line chemotherapy for metastatic colorectal cancer. With current dosing regimens, axitinib plus FOLFOX or FOLFIRI seems to be less well tolerated than bevacizumab-based regimens.
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN. Electronic address: jbendell@tnonc.com.
authors.forename: Johanna C
authors.initials: JC
authors.lastname: Bendell
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.forename: Anna
authors.initials: A
authors.lastname: Swieboda-Sadlej
authors.forename: Carlo
authors.initials: C
authors.lastname: Barone
authors.forename: Zev A
authors.initials: ZA
authors.lastname: Wainberg
authors.forename: Jong Gwang
authors.initials: JG
authors.lastname: Kim
authors.forename: Carles
authors.initials: C
authors.lastname: Pericay
authors.forename: Davide
authors.initials: D
authors.lastname: Pastorelli
authors.forename: Jamal
authors.initials: J
authors.lastname: Tarazi
authors.forename: Brad
authors.initials: B
authors.lastname: Rosbrook
authors.forename: Joanna
authors.initials: J
authors.lastname: Bloom
authors.forename: Alejandro D
authors.initials: AD
authors.lastname: Ricart
authors.forename: Sinil
authors.initials: S
authors.lastname: Kim
authors.forename: Alberto F
authors.initials: AF
authors.lastname: Sobrero
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; 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; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; 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; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D055815:Young Adult
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D007093:Imidazoles; D007191:Indazoles; D009944:Organoplatinum Compounds; D000068258:Bevacizumab; D000077784:Axitinib; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Chemotherapy; Irinotecan; Oxaliplatin; Second-line; VEGF