Location of colon cancer (right-sided versus left-sided) as a prognostic factor and a predictor of benefit from cetuximab in NCIC CO.17

西妥昔单抗 医学 克拉斯 内科学 结直肠癌 肿瘤科 危险系数 比例危险模型 表皮生长因子受体 脾曲 耐火材料(行星科学) 胃肠病学 癌症 置信区间 结肠镜检查 生物 天体生物学
作者
Stephanie Yasmin Brule,Derek J. Jonker,Christos S. Karapetis,Chris O’Callaghan,Malcolm J. Moore,Ralph Wong,Niall C. Tebbutt,C.R. Underhill,Desmond Yip,John Zalcberg,Dongsheng Tu,Rachel Goodwin
出处
期刊:European Journal of Cancer [Elsevier]
卷期号:51 (11): 1405-1414 被引量:273
标识
DOI:10.1016/j.ejca.2015.03.015
摘要

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.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).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].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.
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