Peeters Marc, Karthaus Meinolf, Rivera Fernando, Terwey Jan-Henrik, Douillard Jean-Yves
Department of Oncology, Antwerp University Hospital, Wilrijkstraat 10, 2650, Edegem, Belgium,
Drugs. 2015 May;75(7):731-48. doi: 10.1007/s40265-015-0386-x.
Tumour biomarker status is being used more and more frequently to guide treatment decisions in patients with metastatic colorectal cancer (mCRC). Continued cycles of hypothesis generation and biomarker testing in retrospective, prospective-retrospective and prospective analyses from studies of the epidermal growth factor (EGFR)-targeted monoclonal antibodies (mAbs), panitumumab and cetuximab, have resulted in improved patient selection in mCRC. Initial data suggested EGFR-targeted mAb treatment should be limited to patients with KRAS exon 2 wild-type (WT) tumours, but the availability of tumour samples from large phase III studies permitted evaluation of additional potential biomarkers of activity for these agents. Subsequent analyses further refined the target population to those patients whose tumours were WT for KRAS and NRAS exons 2, 3 and 4 (i.e., those with RAS WT status). Here, we review key clinical data for panitumumab in mCRC across the lines of treatment, assessing in detail the impact of more comprehensive RAS selection on patient outcomes. Panitumumab data across first- to third-line therapy consistently demonstrate that by testing tumour RAS status, it is possible to select patients more likely to benefit from treatment.
肿瘤生物标志物状态越来越频繁地用于指导转移性结直肠癌（mCRC）患者的治疗决策。在针对表皮生长因子（EGFR）的单克隆抗体（mAb）帕尼单抗和西妥昔单抗的研究中，通过回顾性、前瞻性-回顾性和前瞻性分析持续进行假设生成和生物标志物检测的循环，已改善了mCRC患者的选择。初始数据表明，EGFR靶向mAb治疗应限于KRAS外显子2野生型（WT）肿瘤患者，但来自大型III期研究的肿瘤样本使得能够评估这些药物的其他潜在活性生物标志物。随后的分析进一步将目标人群细化为肿瘤KRAS和NRAS外显子2、3和4为WT的患者（即RAS WT状态患者）。在此，我们回顾帕尼单抗在mCRC各治疗线中的关键临床数据，详细评估更全面的RAS选择对患者结局的影响。帕尼单抗在一线至三线治疗中的数据一致表明，通过检测肿瘤RAS状态，可以选择更可能从治疗中获益的患者。
