Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan.
Oncology. 2014;87(1):7-20. doi: 10.1159/000360989. Epub 2014 Jun 24.
Mutations in the KRAS gene have been identified as negative predictors of response to anti-epidermal growth factor receptor (EGFR) monoclonal antibody therapy by patients with metastatic colorectal cancer (mCRC). However, it has been based on the study of mainly Caucasian mCRC patients. This prospective study investigated the relationship between the mutation status of EGFR-related genes including KRAS and the response rate (RR) to cetuximab plus irinotecan therapy in Japanese mCRC patients.
Samples taken from 43 chemotherapy-refractory mCRC patients who had undergone cetuximab plus irinotecan therapy at 11 medical centers in Japan were subjected to direct DNA sequencing to determine the KRAS, BRAF, PIK3CA, NRAS, and AKT1 mutation status. The clinical outcome after the treatment was evaluated for each mutation status.
KRAS mutations were detected in 31.7% of 41 eligible patients. The RR to cetuximab plus irinotecan therapy was found to be 17.9 and 0% in the KRAS wild-type and mutant subgroups, respectively.
Despite the identification of a lower-than-expected RR to treatment by the KRAS wild-type subgroup, KRAS mutation status appears to be a useful predictive marker of response to cetuximab plus irinotecan therapy in Japanese mCRC patients.
KRAS 基因突变已被确定为转移性结直肠癌（mCRC）患者对表皮生长因子受体（EGFR）单克隆抗体治疗反应的负预测因子。然而，这是基于对主要为高加索人 mCRC 患者的研究。本前瞻性研究调查了包括 KRAS 在内的 EGFR 相关基因的突变状态与日本 mCRC 患者接受西妥昔单抗联合伊立替康治疗的反应率（RR）之间的关系。
对来自日本 11 个医学中心的 43 名接受西妥昔单抗联合伊立替康治疗的化疗耐药 mCRC 患者的样本进行直接 DNA 测序，以确定 KRAS、BRAF、PIK3CA、NRAS 和 AKT1 基因突变状态。评估每个突变状态后的治疗临床结局。
在 41 名合格患者中，检测到 KRAS 突变的患者占 31.7%。在 KRAS 野生型和突变亚组中，西妥昔单抗联合伊立替康治疗的 RR 分别为 17.9%和 0%。
尽管 KRAS 野生型亚组的治疗反应率低于预期，但 KRAS 突变状态似乎是日本 mCRC 患者对西妥昔单抗联合伊立替康治疗反应的有用预测标志物。
