title: A randomized phase IIIB trial of chemotherapy, bevacizumab, and panitumumab compared with chemotherapy and bevacizumab alone for metastatic colorectal cancer.
abstract: OBJECTIVE
  Panitumumab, a fully human antibody targeting the epidermal growth factor receptor, is active in patients with metastatic colorectal cancer (mCRC). This trial evaluated panitumumab added to bevacizumab and chemotherapy (oxaliplatin- and irinotecan-based) as first-line treatment for mCRC.
  
  
  METHODS
  Patients were randomly assigned within each chemotherapy cohort to bevacizumab and chemotherapy with or without panitumumab 6 mg/kg every 2 weeks. The primary end point was progression-free survival (PFS) within the oxaliplatin cohort. Tumor assessments were performed every 12 weeks and reviewed centrally.
  
  
  RESULTS
  A total of 823 and 230 patients were randomly assigned to the oxaliplatin and irinotecan cohorts, respectively. Panitumumab was discontinued after a planned interim analysis of 812 oxaliplatin patients showed worse efficacy in the panitumumab arm. In the final analysis, median PFS was 10.0 and 11.4 months for the panitumumab and control arms, respectively (HR, 1.27; 95% CI, 1.06 to 1.52); median survival was 19.4 months and 24.5 months for the panitumumab and control arms, respectively. Grade 3/4 adverse events in the oxaliplatin cohort (panitumumab v control) included skin toxicity (36% v 1%), diarrhea (24% v 13%), infections (19% v 10%), and pulmonary embolism (6% v 4%). Increased toxicity without evidence of improved efficacy was observed in the panitumumab arm of the irinotecan cohort. KRAS analyses showed adverse outcomes for the panitumumab arm in both wild-type and mutant groups.
  
  
  CONCLUSIONS
  The addition of panitumumab to bevacizumab and oxaliplatin- or irinotecan-based chemotherapy results in increased toxicity and decreased PFS. These combinations are not recommended for the treatment of mCRC in clinical practice.
authors.affiliation: David Geffen School of Medicine at UCLA, Santa Monica, CA 90404, USA. jrhecht@mednet.ucla.edu
authors.forename: J Randolph
authors.initials: JR
authors.lastname: Hecht
authors.forename: Edith
authors.initials: E
authors.lastname: Mitchell
authors.forename: Tarek
authors.initials: T
authors.lastname: Chidiac
authors.forename: Carroll
authors.initials: C
authors.lastname: Scroggin
authors.forename: Christopher
authors.initials: C
authors.lastname: Hagenstad
authors.forename: David
authors.initials: D
authors.lastname: Spigel
authors.forename: John
authors.initials: J
authors.lastname: Marshall
authors.forename: Allen
authors.initials: A
authors.lastname: Cohn
authors.forename: David
authors.initials: D
authors.lastname: McCollum
authors.forename: Philip
authors.initials: P
authors.lastname: Stella
authors.forename: Robert
authors.initials: R
authors.lastname: Deeter
authors.forename: Seta
authors.initials: S
authors.lastname: Shahin
authors.forename: Rafael G
authors.initials: RG
authors.lastname: Amado
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage* / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D000077544:Panitumumab
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077544:Panitumumab; D000077146:Irinotecan; D002166:Camptothecin