title: Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17.
abstract: BACKGROUND
  Right- and left-sided colon cancers (RC, LC) differ with respect to biology, pathology and epidemiology. Previous data suggest a mortality difference between RC and LC. We examined if primary tumour side also predicts for outcome in chemotherapy refractory, metastatic colon cancer (MCC). We also compared RC versus LC as a predictor of efficacy of epidermal growth factor receptor (EGFR) inhibition with cetuximab.
  
  
  METHODS
  Reanalyzing NCIC CO.17 trial (cetuximab versus best supportive care [BSC]), we coded the primary tumour side as RC (caecum to transverse colon) or LC (splenic flexure to rectosigmoid). The association between tumour side and baseline characteristics was assessed. Cox regression models determined factors affecting overall survival (OS) and progression free survival (PFS).
  
  
  RESULTS
  Patients with RC (150/399) had more poorly differentiated, mutant KRAS, mutated PIK3CA and wild-type BRAF tumours, fewer liver and lung metastases, and shorter interval between diagnosis and study entry. Among BSC patients, tumour side was not prognostic for PFS (hazard ratios (HR) 1.07 [0.79-1.44], p = 0.67) or OS (HR 0.96 [0.70-1.31], p = 0.78). Among wild-type KRAS patients, those with LC had significantly improved PFS when treated with cetuximab compared to BSC (median 5.4 versus 1.8 months, HR 0.28 [0.18-0.45], p < 0.0001), whereas those with RC did not (median 1.9 versus 1.9 months, HR 0.73 [0.42-1.27], p = 0.26), [interaction p = 0.002].
  
  
  CONCLUSIONS
  In refractory MCC, tumour location within the colon is not prognostic, but is strongly predictive of PFS benefit from cetuximab therapy. Additional research is needed to understand the molecular differences between RC and LC and their interaction with EGFR inhibition.
authors.affiliation: The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada.
authors.forename: S Y
authors.initials: SY
authors.lastname: Brulé
authors.affiliation: The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; NCIC Clinical Trials Group, Kingston, Canada.
authors.forename: D J
authors.initials: DJ
authors.lastname: Jonker
authors.affiliation: Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, Australia.
authors.forename: C S
authors.initials: CS
authors.lastname: Karapetis
authors.affiliation: NCIC Clinical Trials Group, Kingston, Canada.
authors.forename: C J
authors.initials: CJ
authors.lastname: O'Callaghan
authors.affiliation: Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada.
authors.forename: M J
authors.initials: MJ
authors.lastname: Moore
authors.affiliation: CancerCare Manitoba, Winnipeg, MB, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Wong
authors.affiliation: Austin Health and University of Melbourne, Heidelberg, Australia.
authors.forename: N C
authors.initials: NC
authors.lastname: Tebbutt
authors.affiliation: Border Medical Oncology, Albury, Australia.
authors.forename: Cr
authors.initials: C
authors.lastname: Underhill
authors.affiliation: Canberra and Calvary Hospitals, Canberra, Australia.
authors.forename: D
authors.initials: D
authors.lastname: Yip
authors.affiliation: Division of Cancer Medicine, Peter McCallum Cancer Centre, Melbourne, Australia.
authors.forename: J R
authors.initials: JR
authors.lastname: Zalcberg
authors.affiliation: NCIC Clinical Trials Group, Kingston, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Tu
authors.affiliation: The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada. Electronic address: rgoodwin@ottawahospital.on.ca.
authors.forename: R A
authors.initials: RA
authors.lastname: Goodwin
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D000068818:Cetuximab; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010166:Palliative Care / Q000379:methods; D011379:Prognosis; D012044:Regression Analysis; D015996:Survival Rate
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068818:Cetuximab
keywords: Cetuximab; Colon cancer; Distal; EGFR inhibition; KRAS; Proximal