National Cancer Center Hospital East, Gastrointestinal/Oncology Division, 6-5-1 Kashiwanoha, Kashiwa-shi, Chiba-ken 277-8577, Japan.
Jpn J Clin Oncol. 2011 Feb;41(2):210-6. doi: 10.1093/jjco/hyq229. Epub 2010 Dec 17.
Mutation status of the KRAS gene in tumors has been shown to be a predictive biomarker of response to anti-epidermal growth factor receptor antibody therapy in patients with metastatic colorectal cancer. This retrospective analysis examined the association between efficacy and safety of the fully human anti-epidermal growth factor receptor antibody panitumumab and KRAS mutation status in Japanese metastatic colorectal cancer patients using data from two clinical trials with adherence to good clinical practices.
An exploratory, integrated analysis of data from KRAS evaluable patients enrolled in a Phase 1 study (Study 20040192) and a Phase 2 study (Study 20050216) was performed. Paraffin-embedded tumor samples were analyzed for KRAS status. Primary efficacy endpoint of this analysis was objective tumor response per modified response evaluation criteria in solid tumors; a key secondary endpoint was progression-free survival. Safety endpoints included incidence of adverse events.
Tumor samples with known KRAS status were available from 8 of 13 (62%) metastatic colorectal cancer patients in the Phase 1 study and 16 of 53 patients (30%) in the Phase 2 study. Overall, 14 (58%) patients had wild-type KRAS tumors and 10 (42%) patients had mutated KRAS tumors. Four (17%) patients had a partial response; all responders had tumors with wild-type KRAS. Results of all secondary efficacy endpoints also favored patients with wild-type KRAS. Treatment-related adverse events were predominantly mild to moderate and skin related, and were similar between patients with tumors with wild-type and mutated KRAS in this small patient population.
Mutated KRAS status in tumors of Japanese patients with metastatic colorectal cancer is associated with lack of response to panitumumab therapy.
肿瘤中 KRAS 基因突变状态已被证明是转移性结直肠癌患者对表皮生长因子受体抗体治疗反应的预测生物标志物。本回顾性分析使用符合良好临床实践的两项临床试验的数据，考察了完全人源化抗表皮生长因子受体抗体帕尼单抗的疗效和安全性与 KRAS 突变状态在日本转移性结直肠癌患者中的相关性。
对 KRAS 可评估患者的数据分析进行了探索性的综合分析，这些患者来自一项 1 期研究（研究 20040192）和一项 2 期研究（研究 20050216）。对石蜡包埋的肿瘤样本进行 KRAS 状态分析。该分析的主要疗效终点是根据实体瘤改良疗效评价标准评估的客观肿瘤缓解；关键次要终点是无进展生存期。安全性终点包括不良事件的发生率。
在 1 期研究的 13 例转移性结直肠癌患者中有 8 例（62%）和 2 期研究的 53 例患者中有 16 例（30%）的肿瘤样本具有已知的 KRAS 状态。总的来说，14 例（58%）患者的 KRAS 肿瘤为野生型，10 例（42%）患者的 KRAS 肿瘤为突变型。4 例（17%）患者有部分缓解；所有缓解者的肿瘤均为野生型 KRAS。所有次要疗效终点的结果也都有利于 KRAS 野生型患者。治疗相关不良事件主要为轻度至中度，与皮肤相关，在这个小患者人群中，KRAS 野生型和突变型肿瘤患者的不良事件相似。
日本转移性结直肠癌患者肿瘤的 KRAS 突变状态与帕尼单抗治疗无反应相关。
