Introduction: Right- and left-sided colorectal cancers (CRCs) differ in clinical and molecular characteristics. Some retrospective analyses suggested that patients with right-sided tumors derive less benefit from anti-epidermal growth factor receptor (EGFR) antibodies; however, molecular selection in those studies was not extensive.
Patients and methods: Patients with RAS and BRAF wild-type metastatic CRC (mCRC) who were treated with single-agent anti-EGFRs or with cetuximab-irinotecan (if refractory to previous irinotecan) were included in the study. Differences in outcome between patients with right- and left-sided tumors were investigated.
Results: Of 75 patients, 14 and 61 had right- and left-sided tumors, respectively. None of the right-sided tumors responded according to RECIST, compared with 24 left-sided tumors (overall response rate: 0% vs. 41%; p = .0032), and only 2 patients with right-sided tumors (15%) versus 47 patients with left-sided tumors (80%) achieved disease control (p < .0001). The median duration of progression-free survival was 2.3 and 6.6 months in patients with right-sided and left-sided tumors, respectively (hazard ratio: 3.97; 95% confidence interval: 2.09-7.53; p < .0001).
Conclusion: Patients with right-sided RAS and BRAF wild-type mCRC seemed to derive no benefit from single-agent anti-EGFRs.
Implications for practice: Right- and left-sided colorectal tumors have peculiar epidemiological and clinicopathological characteristics, distinct gene expression profiles and genetic alterations, and different prognoses. This study assessed the potential predictive impact of primary tumor site with regard to anti-epidermal growth factor receptor (EGFR) monoclonal antibody treatment in patients with RAS and BRAF wild-type metastatic colorectal cancer. The results demonstrated the lack of activity of anti-EGFRs in RAS and BRAF wild-type, right-sided tumors, thus suggesting a potential role for primary tumor location in driving treatment choices.
摘要
引言. 右侧和左侧结直肠癌 (CRC) 的临床特征和分子特征都不相同。一些回顾性分析提示右侧肿瘤患者从抗表皮生长因子受体 (EGFR) 抗体治疗的获益较少, 然而这些研究并未广泛开展分子选择。
患者与方法. 本研究纳入了接受抗 EGFR 单药或西妥昔单抗+伊立替康 (既往伊立替康治疗后复发患者) 治疗的 RAS 和 BRAF 野生型转移性 CRC (mCRC) 患者。观察左侧肿瘤和右侧肿瘤患者转归的差异。
结果. 75 例患者中, 14 例为右侧肿瘤, 61 例为左侧肿瘤。根据 RECIST 标准, 无一例右侧肿瘤患者达到缓解, 而 24 例左侧肿瘤患者达到缓解 (总缓解率0% vs. 41%, P=0.003 2); 仅 2 例 (15%) 右侧肿瘤患者达到疾病控制, 而左侧肿瘤患者中有 47 例 (80%) 达到疾病控制 (P<0.000 1)。右侧和左侧肿瘤患者的中位无进展生存分别为 2.3 个月和 6.6 个月 (风险比: 3.97, 95%置信区间: 2.09∼7.53, P<0.000 1)。
结论. 抗 EGFR 单药治疗对于右侧 RAS 和 BRAF 野生型 mCRC 患者似乎没有获益。The Oncologist 2016;21:988–994
对临床实践的提示: 右侧和左侧结直肠癌的流行病学和临床病理学特征各异, 基因表达谱及变异截然不同, 预后也不一样。本研究评估了原发肿瘤部位对 RAS 和 BRAF 野生型转移性结直肠癌患者对抗表皮生长因子受体 (EGFR) 单克隆抗体治疗的潜在预测作用。结果证实抗 EGFR 治疗对 RAS 和 BRAF 野生型右侧肿瘤患者疗效有限, 提示了原发肿瘤部位在治疗选择中具有潜在作用。
Keywords: Anti-EGFR monoclonal antibodies; Left-sided tumor; Metastatic colorectal cancer; Right-sided tumor.
©AlphaMed Press.