Clinical Likelihood of Sporadic Primary EGFR T790M Mutation in EGFR-Mutant Lung Cancer
Clinical Likelihood of Sporadic Primary EGFR T790M Mutation in EGFR-Mutant Lung Cancer
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DOI：
10.1016/j.cllc.2014.09.002
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发表时间：
2015-01-01
影响因子：
3.6
通讯作者：
Lee, Jin Soo
中科院分区：
文献类型：
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作者：
Lee, Youngjoo;Lee, Geon Kook;Lee, Jin Soo
携带散发性原发性EGFR T790 M突变的EGFR突变型肺癌的临床特征与经典EGFR突变型肺癌相似，除了不吸烟者和脑转移的比例过高。此外，任何细胞毒性药物均未显示对该突变肿瘤的敏感性增加。因此，新的治疗策略，包括T790 M靶向药物，需要提高EGFR-TKI在这个population.Background的疗效：据报道，存在的治疗前EGFR T790 M突变可能会降低EGFR酪氨酸激酶抑制剂（TKI）在EGFR突变型肺癌的疗效。然而，与治疗前T790 M突变可能性相关的临床病理特征仍然未知。患者和方法：采用质谱法对携带敏感EGFR突变的晚期非小细胞肺癌患者的124份治疗前组织样本的DNA进行EGFR T790 M突变基因分型。我们比较了24例T790 M患者和100例无或低水平T790 M突变患者的特征。结果：T790 M组与非/低T790 M组在年龄、性别、组织学或初始阶段方面无差异。然而，T790 M组中从不吸烟者明显更多（P = 0.017）。T790 M组的脑转移也更常见（P = 0.036）。铂类、紫杉烷类、吉西他滨和培美曲塞的缓解率在两组之间没有差异。在T790 M组中，4种细胞毒性药物的缓解率无显著差异（P = .809）。在EGFR-TKI治疗期间，T790 M组的中位至进展时间短于无/低T790 M组（分别为4.1个月vs. 11.5个月; P <0.001）。两组从晚期疾病一线治疗开始的中位总生存期相似（分别为31.5个月和36.0个月; P = 0.310）。结论：EGFR T790 M突变型肺癌的临床特征与敏感EGFR突变型肺癌相似，除了不吸烟者和脑转移的比例过高。(C)2015 Elsevier Inc. All rights reserved.
The clinical profile of EGFR-mutant lung cancer carrying sporadic primary EGFR T790M mutation was similar to that of classic EGFR-mutant lung cancer, except for an overrepresentation of never-smokers and brain metastasis. Additionally, any cytotoxic drugs showed no increased sensitivity for this mutant tumor. Thus, novel treatment strategies including T790M-targeting drugs are required to improve the efficacy of EGFR-TKIs in this population.Background: It has been reported that the presence of pretreatment EGFR T790M mutation may reduce the efficacy to EGFR tyrosine kinase inhibitors (TKI) in EGFR-mutant lung cancer. However, clinicopathologic features related to the likelihood of T790M mutation before treatment remains unknown. Patients and Methods: DNA from 124 pretreatment tissue samples from patients with advanced non-small-cell lung cancer carrying sensitive EGFR mutations was genotyped for EGFR T790M mutation with mass spectrometry. We compared the characteristics of 24 T790M patients and 100 patients with no or a low-level T790M mutation. Results: There were no differences in age, sex, histology, or initial stage between T790M and non/low T790M groups. However, there were significantly more never-smokers in the T790M group (P = .017). Brain metastasis was also more common in the T790M group (P = .036). The response rates to platinum, taxane, gemcitabine, and pemetrexed did not differ between the 2 groups. In the T790M group, the response rates were not significantly different among the 4 cytotoxic drugs (P = .809). The median time to progression during EGFR-TKI therapy was shorter in the T790M group than in the non/low T790M group (4.1 vs. 11.5 months, respectively; P < .001). The median overall survival from the start of first-line treatment of advanced disease was similar in both groups (31.5 vs. 36.0 months, respectively; P = .310). Conclusion: The clinical features of EGFR T790M-mutant lung cancer were similar to those of sensitive EGFR-mutant lung cancer, except for the overrepresentation of never-smokers and brain metastasis. (C) 2015 Elsevier Inc. All rights reserved.