Activity of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Patients with Non-small Cell Lung Cancer Harboring Rare Epidermal Growth Factor Receptor Mutations
Activity of Epidermal Growth Factor Receptor-Tyrosine Kinase Inhibitors in Patients with Non-small Cell Lung Cancer Harboring Rare Epidermal Growth Factor Receptor Mutations
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DOI：
10.1097/jto.0b013e318227e8c6
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发表时间：
2011-11-01
影响因子：
20.4
通讯作者：
Barberis, Massimo
中科院分区：
文献类型：
--
作者：
De Pas, Tommaso;Toffalorio, Francesca;Barberis, Massimo
简介：表皮生长因子受体（EGFR）的突变已被证明可以预测EGFR-酪氨酸激酶抑制剂（EGFR- tki）、吉非替尼和厄洛替尼的活性。尽管“常见的”EGFR突变，如外显子21的L858R点突变和外显子19的框架内缺失突变，已经明确地与对EGFR- tkis的反应相关，但与许多其他罕见突变对治疗的反应的相关性仍不清楚。在这项研究中，我们报告了用EGFR- tkis治疗含有罕见EGFR突变的晚期非小细胞肺癌患者的结果。方法：对2006 ~ 2010年筛查的681例非小细胞肺癌的罕见突变频率进行调查。外显子18和20的突变，外显子19和21的不常见突变，和/或单个肿瘤中存在不同的突变（复杂突变）被认为是罕见的。结果：99例肿瘤中检测到EGFR突变，占14.5%。18例患者携带罕见突变，其中10例患者接受厄洛替尼或吉非替尼治疗。临床结果根据文献逐一描述。值得注意的是，我们发现了两个以前从未发现过的EGFR突变和一个对EGFR- tkis的未知反应。结论：吉非替尼和厄洛替尼根据EGFR突变类型的不同具有不同的抗肿瘤活性。报告含有罕见突变的病例可以支持这类患者的决策过程。
Introduction: Mutations of the epidermal growth factor receptor (EGFR) have been proven to predict activity of the EGFR-tyrosine kinase inhibitors (EGFR-TKI), gefitinib and erlotinib. Although the "common" EGFR mutations, such as the L858R point mutation in exon 21 and the in-frame deletional mutation in exon 19, have been definitively associated with response to EGFR-TKIs, the correlation with response to treatment for many other rarer mutations is still unclear. In this study, we report the results of treating patients with advanced non-small cell lung cancer harboring rare EGFR mutations treated with EGFR-TKIs.Methods: The frequency of rare mutations has been investigated in 681 cases of non-small cell lung cancer screened between 2006 and 2010. Mutations in exons 18 and 20, uncommon mutations in exons 19 and 21, and/or the presence of different mutations in a single tumor (complex mutations) were considered rare.Results: EGFR mutations were detected in 99 tumors (14.5%). Eighteen cases carried rare mutations, and 10 of these patients were treated with erlotinib or gefitinib. The clinical outcome was described case by case with references to the literature. Of note, we found two EGFR mutations never identified before and one of unknown response to EGFR-TKIs.Conclusions: Gefitinib and erlotinib have different antitumor activity according to the type of the EGFR mutation borne. Report of cases harboring rare mutations can support the decision-making process in this subset of patients.