Sakata Shinichiro, Larson David W
Department of Surgery, Division of Colon and Rectal Surgery, Mayo Clinic, 200 first st sw, Rochester, MN 55905, USA.
Department of Surgery, Division of Colon and Rectal Surgery, Mayo Clinic, 200 first st sw, Rochester, MN 55905, USA.
Surg Oncol Clin N Am. 2022 Apr;31(2):255-264. doi: 10.1016/j.soc.2021.11.006. Epub 2022 Mar 9.
Metastatic colorectal cancer (mCRC) is incurable in patients with unresectable disease. For most patients, the primary treatment is palliative systemic chemotherapy. Genomic profiling is used to detect specific genetic mutations that may offer selected patients a modest survival benefit with targeted therapy. Patients with mCRC with KRAS/NRAS/BRAF wild-type left-sided tumors may benefit from epidermal growth factor receptor (EGFR) inhibition with either cetuximab or panitumumab, in conjunction with chemotherapy. EGFR inhibitors can extend survival by 6 months compared with chemotherapy alone. The vascular endothelial growth factor (VEGF) inhibitor bevacizumab can serve as an alternative to EGFR inhibitors in right-sided tumors or second-line therapy. Many patients will have RAS mutations, and targeted therapies will not provide any benefit. The PRIME trial demonstrated that the addition of panitumumab to FOLFOX was associated with reduced overall survival. Patients with BRAF mutations do not benefit from targeted therapy unless a BRAF inhibitor supplements treatment. Triple combination therapy with cetuximab, the BRAF inhibitor encorafenib, and the MEK kinase inhibitor binimetinib has extended overall survival by about 3 months compared with chemotherapy alone. Finally, for the minority patients with microsatellite instability (MSI) high/mismatch repair (MMR) deficient tumors, either due to Lynch syndrome or sporadic mutations, immunotherapy is recommended as first-line treatment. The KEYNOTE-177 trial demonstrated that therapy with single-agent pembrolizumab improved progression-free survival by 8 months compared with FOLFOX or FOLFIRI and with or without EGFR inhibition. At this time, targeted therapy should only be used in patients with unresectable metastatic disease.
转移性结直肠癌（mCRC）对于无法切除的患者来说是无法治愈的。对于大多数患者，主要治疗方法是姑息性全身化疗。基因检测用于检测特定的基因突变，这些突变可能为部分患者提供适度的生存获益，采用靶向治疗。患有KRAS/NRAS/BRAF野生型左侧肿瘤的mCRC患者可能受益于西妥昔单抗或帕尼单抗联合化疗对表皮生长因子受体（EGFR）的抑制作用。与单纯化疗相比，EGFR抑制剂可将生存期延长6个月。血管内皮生长因子（VEGF）抑制剂贝伐单抗可作为右侧肿瘤或二线治疗中EGFR抑制剂的替代药物。许多患者会有RAS突变，靶向治疗不会带来任何益处。PRIME试验表明，在FOLFOX方案中加入帕尼单抗与总生存期降低相关。BRAF突变的患者除非补充BRAF抑制剂进行治疗，否则无法从靶向治疗中获益。与单纯化疗相比，西妥昔单抗、BRAF抑制剂恩考芬尼和MEK激酶抑制剂比美替尼三联联合疗法使总生存期延长了约3个月。最后，对于少数由于林奇综合征或散发性突变导致微卫星高度不稳定（MSI）/错配修复（MMR）缺陷肿瘤的患者，推荐免疫疗法作为一线治疗。KEYNOTE-177试验表明，与FOLFOX或FOLFIRI以及有无EGFR抑制相比，单药帕博利珠单抗治疗可将无进展生存期提高8个月。目前，靶向治疗仅应用于无法切除的转移性疾病患者。
