F.A.C.P., The University of Texas MD Anderson Cancer Center, Department of Gastrointestinal Medical Oncology, 1515 Holcombe Blvd, Box 0426, Houston, Texas 77030, USA.
Oncologist. 2010;15(1):73-84. doi: 10.1634/theoncologist.2009-0167. Epub 2010 Jan 12.
Targeted biologic agents have an established role in treating metastatic colorectal cancer (mCRC). Bevacizumab, a recombinant monoclonal antibody against the vascular endothelial growth factor ligand is approved by the U.S. Food and Drug Administration (FDA) for bevacizumab-naïve patients. Cetuximab, a chimeric monoclonal antibody (mAb) against the epidermal growth factor receptor (EGFR) is FDA approved as a single agent, or in combination with irinotecan, in both irinotecan-naïve and refractory patients, and has additional efficacy in combination with oxaliplatin. Panitumumab, a fully human EGFR mAb, is FDA approved as a single agent in refractory patients but has additional efficacy in combination with chemotherapy. After reaching a temporary therapeutic plateau of FDA-approved agents for the treatment of mCRC, pivotal results have developed that critically affect the care for these patients. Correlative data from randomized trials of EGFR inhibitors across disease settings have demonstrated higher response rates, specifically for patients with wild-type K-RAS tumors. The interpretation of the B-RAF mutation and other molecular markers may further define the appropriateness of anti-EGFR therapy. Recent literature revealed that the first-line use of combined anti-EGFR therapy plus bevacizumab resulted in inferior outcomes and additional toxicities. Furthermore, the role of biologic agents for locally advanced colon cancer cannot be advocated at this time. With impending changes in the health care system, the economic impact of mAbs will continue to be scrutinized. Hence, as the significance of molecular markers continues to develop, their role as it pertains to the appropriate use of biologic agents in the treatment of mCRC will continue to evolve.
靶向生物制剂在治疗转移性结直肠癌（mCRC）方面具有重要作用。贝伐珠单抗是一种针对血管内皮生长因子配体的重组单克隆抗体，已被美国食品和药物管理局（FDA）批准用于贝伐珠单抗初治患者。西妥昔单抗是一种针对表皮生长因子受体（EGFR）的嵌合单克隆抗体（mAb），已被 FDA 批准作为单药治疗或与伊立替康联合用于初治和难治性患者，并且与奥沙利铂联合具有额外的疗效。帕尼单抗是一种完全人源化的 EGFR mAb，已被 FDA 批准用于难治性患者，但与化疗联合具有额外的疗效。在达到 FDA 批准的治疗 mCRC 药物的临时治疗平台后，关键结果已经出现，这对这些患者的治疗产生了重大影响。来自 EGFR 抑制剂在不同疾病环境下的随机试验的相关数据表明，更高的反应率，特别是对于野生型 K-RAS 肿瘤患者。B-RAF 突变和其他分子标志物的解释可能进一步确定抗 EGFR 治疗的适宜性。最近的文献表明，一线使用联合抗 EGFR 治疗加贝伐珠单抗导致结局恶化和额外的毒性。此外，目前不能提倡将生物制剂用于局部晚期结肠癌。随着医疗保健系统的即将发生变化，mAbs 的经济影响将继续受到审查。因此，随着分子标志物的意义不断发展，它们在治疗 mCRC 中作为生物制剂的适当使用的作用将继续演变。
