Masuishi Toshiki, Muro Kei
Dept. of Clinical Oncology, Aichi Cancer Center Hospital.
Gan To Kagaku Ryoho. 2016 Apr;43(4):408-12.
The efficacy of molecular-targeted agent combinations for the treatment of metastatic colorectal cancer has become increasingly evident over recent years, although none of these combinations have been recognized yet as a standard therapy. The intention here is to provide a synopsis of current progress in this developing area by reviewing existing publications and ongoing clinical trials. While bevacizumab plus anti-EGFR agents exhibit detrimental effects in first-line setting , a combination of bevacizumab with erlotinib has been suggested as an effective maintenance therapy. Dabrafenib plus panitumumab in combination with trametinib and encorafenib plus cetuximab in combination with alpelisib, are very promising combination treatments and are currently being developed in clinical trials for patients with BRAF mutant-type tumors. An earlier nonclinical trial suggested that a combination of panitumumab plus trametinib was effective in patients who were resistant to anti- EGFR agents but developing KRAS- or NRAS-mutated tumors. The HERACLES trial further indicated that a combination of trastuzumab and lapatinib showed promising antitumor effects in patients with emerging HER2 amplification. Other reports suggest that irinotecan and cetuximab in combination with tivantinib were more effective than a combination of irinotecan and cetuximab alone for patients with MET amplification, although further research is needed for this application, as results were based upon the analysis of subgroups. It is clear that data arising from both primary research and clinical trials support the combined use of molecular-targeted drugs in the treatment of metastatic colorectal cancer. As clinical trials progress, it is likely that such treatment combinations will become recognized as standard therapies.
近年来，分子靶向药物联合治疗转移性结直肠癌的疗效日益显著，尽管这些联合方案尚未被公认为标准疗法。本文旨在通过回顾现有文献和正在进行的临床试验，概述这一发展领域的当前进展。虽然贝伐单抗联合抗表皮生长因子受体（EGFR）药物在一线治疗中显示出有害作用，但贝伐单抗与厄洛替尼联合使用已被认为是一种有效的维持治疗方法。达拉非尼联合帕尼单抗，以及曲美替尼联合恩考芬尼联合西妥昔单抗与阿培利司联合使用，都是非常有前景的联合治疗方案，目前正在针对BRAF突变型肿瘤患者进行临床试验。一项早期的非临床试验表明，帕尼单抗联合曲美替尼对那些对抗EGFR药物耐药但发生KRAS或NRAS突变肿瘤的患者有效。HERACLES试验进一步表明，曲妥珠单抗和拉帕替尼联合使用对出现HER2扩增的患者显示出有前景的抗肿瘤效果。其他报告表明，对于MET扩增的患者，伊立替康和西妥昔单抗联合替凡替尼比伊立替康和西妥昔单抗单独联合使用更有效，不过由于结果是基于亚组分析，该应用还需要进一步研究。显然，来自基础研究和临床试验的数据都支持在转移性结直肠癌治疗中联合使用分子靶向药物。随着临床试验的进展，这种治疗联合方案很可能会被公认为标准疗法。
