title: Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial.
abstract: OBJECTIVE
  The antiangiogenic agent aflibercept (ziv-aflibercept in the United States) in combination with 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) significantly improved survival in a phase III study of patients with metastatic colorectal cancer (mCRC) previously treated with an oxaliplatin-based regimen. In the present analysis, outcomes were evaluated in prespecified subgroups to assess the consistency of the treatment effect.
  
  
  METHODS
  Patients were randomised to receive FOLFIRI plus aflibercept or placebo every 2weeks until disease progression or unacceptable toxicity occurred. Efficacy and safety outcomes were analysed with respect to demographic and baseline characteristics, and stratification factors (prior bevacizumab treatment and Eastern Cooperative Oncology Group performance status).
  
  
  RESULTS
  Median overall survival (OS, months [95.34% confidence interval (CI)]) for aflibercept versus placebo was 12.5 (10.8-15.5) versus 11.7 (9.8-13.8) in patients with prior bevacizumab treatment and 13.9 (12.7-15.6) versus 12.4 (11.2-13.5) in patients with no prior bevacizumab treatment. The p value for interaction was 0.5668, indicating there was no heterogeneity in these subgroups. For OS and progression-free survival (PFS), there was a significantly greater benefit (at the 2-sided 10% level) of treatment for patients with liver only metastases versus patients with no liver metastases/liver metastases with other organ involvement (p value for interaction: 0.0899 [OS]; 0.0076 [PFS]). There was no evidence of heterogeneity in treatment effect in any of the other subgroups examined.
  
  
  CONCLUSIONS
  The benefits of aflibercept in combination with FOLFIRI in patients with mCRC previously treated with oxaliplatin were maintained across the specified patient subgroups, including in patients with or without prior bevacizumab treatment.
authors.affiliation: Vall d'Hebron University Hospital and Institute of Oncology (VHIO), Universitat Autònoma de Barcelona, Barcelona, Spain. Electronic address: jtabernero@vhio.net.
authors.forename: Josep
authors.initials: J
authors.lastname: Tabernero
authors.affiliation: University Hospitals Leuven and KU Leuven, Belgium.
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.affiliation: Masaryk Memorial Cancer Institute, Brno, Czech Republic.
authors.forename: Radek
authors.initials: R
authors.lastname: Lakomý
authors.affiliation: Fakultni nemocnice v Motole, Praha, Czech Republic.
authors.forename: Jana
authors.initials: J
authors.lastname: Prausová
authors.affiliation: University of Witwatersrand Faculty of Health Sciences, Johannesburg, South Africa.
authors.forename: Paul
authors.initials: P
authors.lastname: Ruff
authors.affiliation: University of Western Australia, Western Australia, Australia.
authors.forename: Guy A
authors.initials: GA
authors.lastname: van Hazel
authors.affiliation: Oncology Research Institute Na.NN.Petrov, St-Petersburg, Russian Federation.
authors.forename: Vladimir M
authors.initials: VM
authors.lastname: Moiseyenko
authors.affiliation: Russells Hall Hospital, Dudley, West Midlands, UK.
authors.forename: David R
authors.initials: DR
authors.lastname: Ferry
authors.affiliation: Monash University, Victoria, Australia.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: McKendrick
authors.affiliation: Sanofi, Vitry-sur-Seine, France.
authors.forename: Karen
authors.initials: K
authors.lastname: Soussan-Lazard
authors.affiliation: Sanofi, Vitry-sur-Seine, France.
authors.forename: Soazig
authors.initials: S
authors.lastname: Chevalier
authors.affiliation: University of Florida, Gainesville, United States.
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Allegra
mesh_terms: D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D003967:Diarrhea / Q000139:chemically induced; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D005221:Fatigue / Q000139:chemically induced; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009503:Neutropenia / Q000139:chemically induced; D011446:Prospective Studies; D040262:Receptors, Vascular Endothelial Growth Factor / Q000008:administration & dosage / Q000009:adverse effects; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D011993:Recombinant Fusion Proteins; C533178:aflibercept; D000068258:Bevacizumab; D000077146:Irinotecan; D040262:Receptors, Vascular Endothelial Growth Factor; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Aflibercept; Bevacizumab; Metastatic colorectal cancer; Performance status; Subgroup analysis; VEGF Trap