雷莫芦单抗未来能否成为有效的mCRC二线治疗选择?

　　RAISE III期研究显示雷莫 芦 单抗（Ramucirumab）能成为有效的mCRC二线治疗选择。RAISE研究受试者清一色是FOLFIRI（氟尿嘧啶、亚叶酸钙和奥沙利铂）方案联合贝伐珠单抗治疗失败的转移性结直肠癌。FOLFIRI联合雷莫芦单抗二线治疗延长了OS和PFS。所以RAISE研究数据干净，各化疗分层各分层指标清晰。所以雷莫 芦 单抗联合FOLFIRI可能是很好的二线治疗选择。目前该药物需要通过FDA、EMA和其他国际监管机构的审批，以获得雷莫芦单抗治疗“转移性结直肠癌”的适应证。

　　从一线到二线的持续肿瘤血管抑制治疗？

　　Tabernero博士指出，有三项研究的数据支持一线到二线持续抑制肿瘤血管生成治疗，这种治疗策略给患者带来了初始获益。TML研究数据揭示了贝伐珠单抗的抗VEGF治疗获益。小样本VELOUR研究中，30%的患者接受过一线贝伐珠单抗治疗，继续用阿柏西普（aflibercept）抑制血管生成，这些患者仍然获益。

　　雷莫芦单抗的获益和毒性如何权衡？

　　Tabernero博士认为，雷莫芦单抗的不良反应可耐受，大多数已观察到的毒性属于常见的VEGF抑制剂或EGFR抑制剂的毒性，诸如高血压和蛋白尿。此外，白细胞减少、血小板减少和疲劳的发生率增加。尽管III~ IV级中性粒细胞减少的发生率增加，中性粒细胞减少性发热的发生率没有变。总之，即使加用雷莫芦单抗治疗增加了毒性，这种毒性也是微不足道的。

访谈原文

　　Oncology Frontier: According to the outcomes of the phase III RAISE trial， do you see ramucirumab as an effective second-line treatment for colorectal cancer in the future?

　　《肿瘤瞭望》：根据RAISE III期研究结果，雷莫芦单抗未来能否成为有效的mCRC二线治疗选择?

　　Dr Tabernero: Basically， that is what the RAISE study has shown. In this particular setting with a very homogenous population of patients with metastatic colorectal cancer where all of them had failed first-line oxaliplatin， fluoropyrimidines and bevacizumab， the addition of ramucirumab to standard FOLFIRI in second-line led to an improvement in overall survival and progression-free survival. So the data from this study is very clean but different from other published studies where the signals have not been as clear for some chemotherapy strategies. So I feel that the addition of ramucirumab to FOLFIRI may be a reasonable option for second-line therapy. We now need to see all of the regulatory approval processes from the FDA， EMA and other international regulatory authorities to promote this indication for patients with metastatic colorectal cancer.

　　Tabernero博士：RAISE研究显示雷莫芦单抗（Ramucirumab）能成为有效的mCRC二线治疗选择。RAISE研究受试者清一色是FOLFIRI（氟尿嘧啶、亚叶酸钙和奥沙利铂）)方案联合贝伐珠单抗治疗失败的转移性结直肠癌。FOLFIRI联合雷莫卢单抗二线治疗延长了OS和PFS。所以RAISE研究数据干净，其他一些已发布的研究的化疗分层的信号不清醒，而RAISE研究不是这样。所以雷莫芦单抗联合FOLFIRI可能是很好的二线治疗选择。目前该药物需要通过FDA、EMA和其他国际监管机构的审批，以获得雷莫芦单抗治疗“转移性结直肠癌”的适应证。

　　Oncology Frontier: When moving from first-line to second-line therapy， do you recommend sustained inhibition of angiogenesis?

　　《肿瘤瞭望》：您是否建议从一线到二线的持续肿瘤血管抑制治疗？

　　Dr Tabernero: There are several clinical trials that support continuing angiogenesis inhibition is of initial benefit. We also have the data from the TML study with bevacizumab that also very clearly showed benefit for VEGF inhibition. Finally， in a small population of the VELOUR study with aflibercept， 30% of patients had also received bevacizumab in the first-line and in this proportion of patients there was also a benefit in continuing angiogenesis inhibition. So there are three pieces of information that support this strategy of continued angiogenesis inhibition.

　　Tabernero博士：有三项研究的数据支持继续抑制肿瘤血管生成治疗，这种治疗策略给患者带来了初始获益。TML研究数据揭示了贝伐珠单抗的抗VEGF治疗获益。小样本VELOUR研究，30%的患者接受过一线贝伐珠单抗治疗，这些患者继续用阿柏西普（aflibercept）抑制血管生成仍然获益。

　　Oncology Frontier: Can you compare and contrast the benefits versus toxicityof ramucirumab therapy?

　　《肿瘤瞭望》：雷莫芦单抗的获益和毒性如何权衡？

　　Dr Tabernero: The safety profile of these agents including ramucirumab is quite acceptable. Most of the toxicities that have been observed are those we would expect for VEGF inhibition or EGFR inhibition such as hypertension and proteinuria. Also， in this case， there is an increase in the conventional toxicities that chemotherapy produces like neutropenia， thrombocytopenia and fatigue. Nevertheless， it is important to mention that even though there is an increased rate of gradeIII/IV neutropenia， the rate of febrile neutropenia is the same. In summary， although there is an increase in toxicity with the addition of ramucirumab， this toxicity is marginal.

　　Tabernero博士：雷莫芦单抗不良反应可耐受，大多数已观察到的毒性属于常见的VEGF抑制剂或EGFR抑制剂的毒性，诸如高血压和蛋白尿。此外，白细胞减少、血小板减少和疲劳的发生率增加。尽管III~ IV级中性粒细胞减少的发生率增加，中性粒细胞减少性发热的发生率是相同的。总之，即使加用雷莫芦单抗治疗增加了毒性，这种毒性也是微不足道的。