title: Response-independent survival benefit in metastatic colorectal cancer: a comparative analysis of N9741 and AVF2107.
abstract: OBJECTIVE
  In the phase III study AVF2107g, bevacizumab (BV) demonstrated a survival benefit when added to irinotecan, fluorouracil, and leucovorin (IFL) in first-line metastatic colorectal cancer (mCRC). In a parallel phase III study, Intergroup N9741, oxaliplatin plus fluorouracil and leucovorin (FOLFOX) also demonstrated a survival benefit compared with IFL. As these two superior therapies have differing mechanisms of action, we explored whether the improved survival associated with the superior therapy was dependent on tumor response.
  
  
  METHODS
  For these retrospective, exploratory analyses, patients were defined as responders or nonresponders by whether complete or partial response was achieved with first-line therapy.
  
  
  RESULTS
  Compared with IFL alone, BV plus IFL and FOLFOX each demonstrated statistically significant improvements in progression-free survival (PFS) and overall survival (OS) regardless of objective tumor response. BV-treated nonresponders had a hazard ratio (HR) of 0.63 (P = .0001) for PFS and 0.76 (P = .0188) for OS compared with IFL-treated nonresponders. FOLFOX-treated nonresponders had an HR of 0.75 (P = .0029) for PFS and 0.74 (P = .0030) for OS compared with IFL-treated nonresponders.
  
  
  CONCLUSIONS
  In both AVF2107g and N9741, objective response did not predict the magnitude of PFS or OS benefit from the superior therapy; nonresponders, despite a poorer prognosis than responders, achieved extended PFS and OS from BV plus IFL or FOLFOX compared with IFL. On the basis of these data, tumor response in metastatic colorectal cancer is not a necessary factor for a therapy to provide benefit to an individual patient.
authors.affiliation: Mayo Clinic College of Medicine, 200 First St SW, Rochester, MN 55905, USA. grothey.axel@mayo.edu
authors.forename: Axel
authors.initials: A
authors.lastname: Grothey
authors.forename: Eric E
authors.initials: EE
authors.lastname: Hedrick
authors.forename: Robert D
authors.initials: RD
authors.lastname: Mass
authors.forename: Somnath
authors.initials: S
authors.lastname: Sarkar
authors.forename: Sam
authors.initials: S
authors.lastname: Suzuki
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Herbert I
authors.initials: HI
authors.lastname: Hurwitz
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000068258:Bevacizumab; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D015337:Multicenter Studies as Topic; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D016019:Survival Analysis
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000068258:Bevacizumab; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin