title: Final results from a randomized phase 3 study of FOLFIRI {+/-} panitumumab for second-line treatment of metastatic colorectal cancer.
abstract: BACKGROUND
  The study 20050181 demonstrated significant improvements in progression-free survival (PFS), objective response, and a nonsignificant trend toward increased overall survival (OS) with panitumumab-FOLFIRI versus FOLFIRI alone for second-line wild-type (WT) KRAS metastatic colorectal cancer (mCRC). Updated long-term data from a prespecified descriptive analysis are reported.
  
  
  METHODS
  Patients receiving one prior mCRC treatment were randomly assigned (1:1) to panitumumab (6.0 mg/kg)-FOLFIRI versus FOLFIRI every 2 weeks. Co-primary end points (PFS and OS) were prospectively analyzed by tumor KRAS status.
  
  
  RESULTS
  One thousand one hundred and eighty-six patients were randomly assigned. In patients with WT KRAS tumors, panitumumab-FOLFIRI significantly improved PFS versus FOLFIRI [median 6.7 versus 4.9 months; hazard ratio (HR) 0.82 [95% confidence interval (CI) 0.69, 0.97]; P = 0.023]. A trend toward longer OS was observed (median 14.5 versus 12.5 months; HR 0.92 [95% CI 0.78, 1.10]; P = 0.37). Response rates improved from 10% to 36% (P < 0.0001). From post hoc analyses in patients receiving prior oxaliplatin-bevacizumab, panitumumab-FOLFIRI improved PFS (median 6.4 versus 3.7 months; HR 0.58 [95% CI 0.37, 0.90]; P = 0.014). PFS and OS appeared longer for worst-grade skin toxicity of 2-4, versus 0-1 or FOLFIRI. Safety results were as previously reported and consistent with the known toxicities with anti-epidermal growth factor receptor therapy.
  
  
  CONCLUSIONS
  These data confirm the primary efficacy and safety findings of this trial and support panitumumab-FOLFIRI as a second-line treatment of WT KRAS mCRC.
authors.affiliation: Department of Oncology, University Hospital Antwerp, Antwerp, Belgium.
authors.forename: M
authors.initials: M
authors.lastname: Peeters
authors.forename: T J
authors.initials: TJ
authors.lastname: Price
authors.forename: A
authors.initials: A
authors.lastname: Cervantes
authors.forename: A F
authors.initials: AF
authors.lastname: Sobrero
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
authors.forename: Y
authors.initials: Y
authors.lastname: Hotko
authors.forename: T
authors.initials: T
authors.lastname: André
authors.forename: E
authors.initials: E
authors.lastname: Chan
authors.forename: F
authors.initials: F
authors.lastname: Lordick
authors.forename: C J A
authors.initials: CJ
authors.lastname: Punt
authors.forename: A H
authors.initials: AH
authors.lastname: Strickland
authors.forename: G
authors.initials: G
authors.lastname: Wilson
authors.forename: T E
authors.initials: TE
authors.lastname: Ciuleanu
authors.forename: L
authors.initials: L
authors.lastname: Roman
authors.forename: E
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Y
authors.initials: Y
authors.lastname: Tian
authors.forename: R
authors.initials: R
authors.lastname: Sidhu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008113:Liver Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D000077544:Panitumumab; D011788:Quality of Life; D012871:Skin Diseases / Q000139:chemically induced; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D000077544:Panitumumab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: FOLFIRI; antibody; chemotherapy; metastatic colorectal cancer; panitumumab