S Y Brulé1, D J Jonker2, C S Karapetis3, C J O'Callaghan4, M J Moore5, R Wong6, N C Tebbutt7, Cr Underhill8, D Yip9, J R Zalcberg10, D Tu4, R A Goodwin11. 1. The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada. 2. The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada; NCIC Clinical Trials Group, Kingston, Canada. 3. Flinders Medical Centre and Flinders Centre for Innovation in Cancer, Flinders University, Adelaide, Australia. 4. NCIC Clinical Trials Group, Kingston, Canada. 5. Princess Margaret Cancer Center, University Health Network, University of Toronto, Toronto, Canada. 6. CancerCare Manitoba, Winnipeg, MB, Canada. 7. Austin Health and University of Melbourne, Heidelberg, Australia. 8. Border Medical Oncology, Albury, Australia. 9. Canberra and Calvary Hospitals, Canberra, Australia. 10. Division of Cancer Medicine, Peter McCallum Cancer Centre, Melbourne, Australia. 11. The Ottawa Hospital Research Institute, University of Ottawa, Ottawa, Canada. Electronic address: rgoodwin@ottawahospital.on.ca.
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]. CONCLUSION: 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.
RCT Entities:
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 KRASpatients, 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]. CONCLUSION: 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: Jonathan M Loree; Allan A L Pereira; Michael Lam; Alexandra N Willauer; Kanwal Raghav; Arvind Dasari; Van K Morris; Shailesh Advani; David G Menter; Cathy Eng; Kenna Shaw; Russell Broaddus; Mark J Routbort; Yusha Liu; Jeffrey S Morris; Rajyalakshmi Luthra; Funda Meric-Bernstam; Michael J Overman; Dipen Maru; Scott Kopetz Journal: Clin Cancer Res Date: 2017-11-27 Impact factor: 12.531