液体活检在奥希替尼获得性耐药的患者血浆中检测 EGFR 驱动基因、T790M 突变和 EGFR 扩增的临床应用
Clinical utility of liquid biopsy for EGFR driver, T790M mutation and EGFR amplification in plasma in patients with acquired resistance to afatinib.
机构信息
Department of Thoracic Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.
Current Address: Department of Thoracic Oncology, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
出版信息
BMC Cancer. 2021 Jan 12;21(1):57. doi: 10.1186/s12885-020-07777-2.
BACKGROUND
Cell-free DNA (cfDNA) genotyping in plasma using the cobas EGFR Mutation Test v2 (cobas) is the first liquid biopsy as a companion diagnosis to identify the EGFR T790M mutation (T790M) after the failure of treatment of EGFR-tyrosine kinase inhibitors (TKIs) (1st generation, gefitinib [G] and erlotinib [E] and 2nd generation, afatinib [A]). This study investigated the clinical utility of a liquid biopsy for patients who acquired resistance to afatinib.
METHODS
We prospectively collected plasma from 51 patients who had acquired resistance to afatinib between April 2015 and November 2016 to evaluate the frequency of T790M by cobas and digital droplet PCR (UMIN000025112). Additionally, we retrospectively reviewed 38 patients who tested by cobas in plasma after G/E failure to compare for T790M detection between A and with G/E.
RESULTS
The detection rate of EGFR-driver and T790M in plasma in patients treated with A (A group) as a first-line EGFR-TKI was lower than with G/E followed by A (G/E→A group), although the differences were not significant (EGFR-driver: 41% [A] vs. 67% [G/E→A], P=0.1867; and T790M: 8% [A] vs. 17% [G/E→A], P=0.5798). In first-line setting, the detection rate for EGFR-driver and T790M in plasma by cobas was lower in A group than in G/E group, although there was no significant difference (EGFR-driver: 34% [A] vs. 52% [G/E], P=0.2072; and T790M: 10% [A] vs. 27% [G/E], P=0.1161).
CONCLUSION
The detection of EGFR-driver and T790M in plasma by cobas in patients treated with afatinib might be lower than with G/E in a real-world setting.
背景
使用 cobas EGFR Mutation Test v2（cobas）对血浆中的无细胞 DNA（cfDNA）进行基因分型是液体活检的首例伴随诊断，用于在 EGFR 酪氨酸激酶抑制剂（1 代，吉非替尼[G]和厄洛替尼[E]和 2 代，阿法替尼[A]）治疗失败后识别 EGFR T790M 突变（T790M）。本研究旨在探讨液体活检在对阿法替尼产生耐药的患者中的临床应用价值。
方法
我们前瞻性地收集了 51 例在 2015 年 4 月至 2016 年 11 月期间对阿法替尼产生耐药的患者的血浆，以通过 cobas 和数字液滴 PCR（UMIN000025112）评估 T790M 的频率。此外，我们回顾性地分析了 38 例在 G/E 失败后用 cobas 在血浆中检测的患者，以比较 A 与 G/E 检测 T790M 的结果。
结果
作为一线 EGFR-TKI 治疗的阿法替尼组（A 组）患者血浆中 EGFR 驱动基因和 T790M 的检出率低于吉非替尼/厄洛替尼后继以阿法替尼组（G/E→A 组），尽管差异无统计学意义（EGFR 驱动基因：41%[A] vs. 67%[G/E→A]，P=0.1867；T790M：8%[A] vs. 17%[G/E→A]，P=0.5798）。在一线治疗中，A 组血浆中 EGFR 驱动基因和 T790M 的 cobas 检测率低于吉非替尼/厄洛替尼组，但无统计学差异（EGFR 驱动基因：34%[A] vs. 52%[G/E]，P=0.2072；T790M：10%[A] vs. 27%[G/E]，P=0.1161）。
结论
在真实世界环境中，阿法替尼治疗患者的 cobas 血浆 EGFR 驱动基因和 T790M 的检测率可能低于吉非替尼/厄洛替尼。
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