title: Comparison of FOLFIRI with or without cetuximab in patients with resected stage III colon cancer; NCCTG (Alliance) intergroup trial N0147.
abstract: BACKGROUND
  Two arms with FOLFIRI, with or without cetuximab, were initially included in the randomized phase III intergroup clinical trial NCCTG (North Central Cancer Treatment Group) N0147. When other contemporary trials demonstrated no benefit to using irinotecan as adjuvant therapy, the FOLFIRI-containing arms were discontinued. We report the clinical outcomes for patients randomized to FOLFIRI with or without cetuximab.
  
  
  METHODS
  After resection, patients were randomized to 12 biweekly cycles of FOLFIRI, with or without cetuximab. KRAS (Kirsten rat sarcoma viral oncogene homolog) mutation status was retrospectively determined in a central lab. The primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS) and toxicity.
  
  
  RESULTS
  One hundred and six patients received FOLFIRI and 40 received FOLFIRI plus cetuximab. Median follow-up was 5.95 years (range, 0.1-7.0 years). The addition of cetuximab showed a trend toward improved DFS (hazard ratio [HR], 0.53; 95% CI, 0.26-1.1; P = .09) and OS (HR, 0.45; 95% CI, 0.17-1.16; P = .10) in the overall group, regardless of KRAS status, and in patients with wild type KRAS. Grade ≥ 3 nonhematologic adverse effects were significantly increased in the cetuximab versus FOLFIRI-alone arm (68% vs. 46%; P = .02). Adjuvant FOLFIRI resulted in a 3-year DFS less than that expected for FOLFOX.
  
  
  CONCLUSIONS
  In this small randomized subset of patients with resected stage III colon cancer, the addition of cetuximab to FOLFIRI was associated with a nonsignificant trend toward improved DFS and OS. Nevertheless, considering the limitations of this analysis, FOLFOX without the addition of a biologic agent remains the standard of care for adjuvant therapy in resected stage III colon cancer.
authors: Department of Oncology, Mayo Clinic Rochester, Rochester, MN.
authors: Jocelin
authors: J
authors: Huang
authors: Lehigh Valley Hospital, Allentown, PA.
authors: Suresh G
authors: SG
authors: Nair
authors: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.
authors: Michelle R
authors: MR
authors: Mahoney
authors: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.
authors: Garth D
authors: GD
authors: Nelson
authors: Department of Oncology, Karmanos Cancer Institute, Detroit, MI.
authors: Anthony F
authors: AF
authors: Shields
authors: Division of Hematology and Oncology, Vanderbilt University Medical Center, Nashville, TN.
authors: Emily
authors: E
authors: Chan
authors: Department of Oncology, The Ohio State University Wexner Medical Center, Columbus, OH.
authors: Richard M
authors: RM
authors: Goldberg
authors: Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, British Columbia, Canada.
authors: Sharlene
authors: S
authors: Gill
authors: Surgical Oncology Associates of South Texas, San Antonio, TX.
authors: Morton S
authors: MS
authors: Kahlenberg
authors: Siouxland Hematology Oncology Associates, Sioux City, IA.
authors: James T
authors: JT
authors: Quesenberry
authors: Department of Oncology, Mayo Clinic Rochester, Rochester, MN.
authors: Stephen N
authors: SN
authors: Thibodeau
authors: Department of Oncology, Mayo Clinic Rochester, Rochester, MN.
authors: Thomas C
authors: TC
authors: Smyrk
authors: Department of Oncology, Mayo Clinic Rochester, Rochester, MN.
authors: Axel
authors: A
authors: Grothey
authors: Department of Oncology, Mayo Clinic Rochester, Rochester, MN.
authors: Frank A
authors: FA
authors: Sinicrope
authors: Illinois Oncology Research Association Community Clinical Oncology Program, Peoria, IL.
authors: Thomas A
authors: TA
authors: Webb
authors: Ochsner Community Clinical Oncology Program, New Orleans, LA.
authors: Gist H
authors: GH
authors: Farr
authors: Mayo Clinic Arizona, Scottsdale, AZ.
authors: Barbara A
authors: BA
authors: Pockaj
authors: University of Hawaii Cancer Center Community Clinical Oncology Program, Honolulu, HI.
authors: Jeffrey L
authors: JL
authors: Berenberg
authors: Clinical Investigations Branch, Cancer Therapy Evaluation Program, Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD.
authors: Margaret
authors: M
authors: Mooney
authors: Alliance Statistics and Data Center, Mayo Clinic, Rochester, MN.
authors: Daniel J
authors: DJ
authors: Sargent
authors: Department of Oncology, Mayo Clinic Rochester, Rochester, MN. Electronic address: alberts.steven@mayo.edu.
authors: Steven R
authors: SR
authors: Alberts
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / 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; D000068818:Cetuximab; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D015996:Survival Rate; D016896:Treatment Outcome; D018631:ras Proteins / Q000235:genetics*
chemical_list: D061067:Antibodies, Monoclonal, Humanized; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin
keywords: Adjuvant therapy; Disease free survival; Overall survival; Response rate