The emergence of targeted therapies for the treatment of metastatic colorectal cancer (mCRC) has considerably improved survival, but has also resulted in a dilemma of identifying the optimal sequence and combination of various agents in the mCRC treatment landscape. A number of cytotoxic agents, including irinotecan, oxaliplatin, 5-fluorouracil, capecitabine, and TAS-102, are available for treatment of mCRC. Additionally, whereas patients harboring rat sarcoma viral oncogene homolog (RAS)-wild type mCRC can be treated with the anti-epidermal growth factor receptor antibodies cetuximab and panitumumab or antiangiogenic agents (bevacizumab, ziv-aflibercept, and ramucirumab), patients with RAS-mutant mCRC are limited to antiangiogenic agents as biologic options. Regorafenib, a multikinase inhibitor, can be used in both RAS subgroups. As such, the recommended sequence of therapies that should be received by each subgroup must also be considered separately. This review provides an overview of recent clinical data for approved and investigational targeted therapies that have been studied across different mCRC treatment lines and patient subgroups. It also examines emerging trends in the treatment landscape for mCRC, including treatment with immune checkpoint inhibitors and the utilization of genomic profiling.
Implications for practice: Currently, there are no established guidelines for optimal sequencing of cytotoxic or targeted agents in metastatic colorectal cancer (mCRC). This review provides a snapshot of the current mCRC treatment paradigm and examines the latest clinical data that support the utilization of several targeted agents alone or in combination with backbone chemotherapy across different lines of treatment and patient populations, highlighting recommendations for their usage. Recent advances in the treatment landscape are also summarized, including genomic profiling and preliminary results with immune checkpoint inhibitors.
摘要
靶向治疗的出现大大提高了转移性结直肠癌（mCRC）的生存率, 但同时也导致难以识别多种mCRC治疗药物的最佳顺序和组合的困境。包括伊立替康、奥沙利铂、5‐氟尿嘧啶、卡培他滨和TAS‐102在内的多种细胞毒性药物可以用于治疗mCRC。此外, 尽管罹患大鼠肉瘤病毒癌基因同源物（RAS）‐野生型mCRC的患者可以接受抗表皮生长因子受体抗体西妥昔单抗和帕尼单抗或抗血管生成药物（贝伐单抗、阿柏西普和雷莫芦单抗）治疗, 但RAS突变mCRC患者只能接受抗血管生成药物作为生物学治疗。两个RAS亚组中均可使用瑞戈非尼（一种多激酶抑制剂）。因此, 也必须单独考虑每个亚组应接受的治疗的推荐顺序。本次回顾提供了已获批准疗法和研究性靶向治疗（已在不同mCRC治疗线和患者亚组中进行过研究）的最新临床研究数据的概览。本次回顾还考察了mCRC治疗领域的新趋势, 包括使用免疫检查点抑制剂治疗和基因组分析。
对临床实践的启示：目前仍然没有关于细胞毒性或靶向药物治疗转移性结直肠癌（mCRC）的最佳顺序的既定指南。本回顾简要介绍了当前mCRC的治疗方法。我们回顾了支持在不同的治疗线和患者人群中单独使用几种靶向药物或靶向药物与核心化疗药物联合给药的最新临床研究数据, 并重点回顾了关于这些药物的使用建议。此外, 我们还总结了治疗领域的最新进展, 包含基因组分析和使用免疫检查点抑制剂的初步结果。
Keywords: Antineoplastic protocols; Colorectal neoplasms; Combination drug therapy; Investigational therapies; Molecular targeted therapy; Patient selection.
© AlphaMed Press 2017.