根据肺癌患者中存在的敏感表皮生长因子受体突变的 T790M 突变水平评估的临床结果。

Clinical outcome according to the level of preexisting epidermal growth factor receptor T790M mutation in patients with lung cancer harboring sensitive epidermal growth factor receptor mutations.

机构信息

Lung Cancer Branch, Research Institute and Hospital, National Cancer Center, Goyang, Republic of Korea; Department of Medicine, Graduate School, Yonsei University, Seoul, Republic of Korea.

出版信息

Cancer. 2014 Jul 15;120(14):2090-8. doi: 10.1002/cncr.28711. Epub 2014 Apr 15.

DOI:10.1002/cncr.28711

PMID:24737599

Abstract

BACKGROUND

Epidermal growth factor receptor (EGFR) T790M mutation drives acquired drug resistance to EGFR tyrosine kinase inhibitors (EGFR-TKIs) in patients with EGFR-mutant lung cancer. However, it was reported that this mutation may exist before drug exposure. The objective of the current study was to evaluate whether the clinical outcomes are affected by the percentage of preexisting T790M mutations within a tumor.

METHODS

Pretreatment tissues were collected from 124 patients with advanced non-small cell lung cancer with sensitizing EGFR mutations that were detected by direct sequencing. Genotyping for EGFR T790M mutation was further performed using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Patients who were positive for the T790M mutation were divided to 2 subgroups according to T790M mutant signal frequency.

RESULTS

The T790M mutation was found in 31 patients (25.0%). The T790M mutation frequency at which the risk of disease progression after therapy with EGFR-TKIs begins to increase was estimated to be 3.2%. The patients with T790M-positive tumors had a shorter time to disease progression after treatment with EGFR-TKIs (median, 6.3 months vs 11.5 months; P < .001) and overall survival (median, 16.1 months vs 26.5 months; P = .065) compared with those with T790M-negative tumors. Among the T790M-positive patients, the patients with high T790M frequency (9 patients) were found to have a shorter time to disease progression (median, 2.4 months vs 6.7 months; P = .009) and overall survival (median, 9.1 months vs 18.7 months; P = .018) compared with those with low T790M frequency (22 patients).

CONCLUSIONS

A preexisting EGFR T790M mutation was noted in 25% of patients with EGFR-mutant lung cancer. Patients with a high T790M mutation frequency had worse clinical outcomes to EGFR-TKIs than patients with a low T790M mutation frequency.

摘要

背景

表皮生长因子受体（EGFR）T790M 突变导致 EGFR 突变型肺癌患者对 EGFR 酪氨酸激酶抑制剂（EGFR-TKIs）产生获得性耐药。然而，据报道，这种突变可能在药物暴露之前就存在。本研究的目的是评估肿瘤内预先存在的 T790M 突变百分比是否会影响临床结局。

方法

收集了 124 例经直接测序检测到敏感 EGFR 突变的晚期非小细胞肺癌患者的预处理组织。使用基质辅助激光解吸/电离飞行时间质谱法进一步进行 EGFR T790M 突变基因分型。T790M 突变阳性患者根据 T790M 突变信号频率分为 2 个亚组。

结果

31 例患者（25.0%）发现 T790M 突变。预测 EGFR-TKIs 治疗后疾病进展风险开始增加的 T790M 突变频率为 3.2%。与 T790M 阴性肿瘤患者相比，T790M 阳性肿瘤患者在接受 EGFR-TKIs 治疗后的疾病进展时间（中位数 6.3 个月比 11.5 个月；P <.001）和总生存期（中位数 16.1 个月比 26.5 个月；P =.065）更短。在 T790M 阳性患者中，高频 T790M（9 例）患者的疾病进展时间（中位数 2.4 个月比 6.7 个月；P =.009）和总生存期（中位数 9.1 个月比 18.7 个月；P =.018）均短于低频 T790M（22 例）。