Del Re Marzia, Petrini Iacopo, Mazzoni Francesca, Valleggi Simona, Gianfilippo Giulia, Pozzessere Daniele, Chella Antonio, Crucitta Stefania, Rofi Eleonora, Restante Giuliana, Miccoli Mario, Garassino Marina Chiara, Danesi Romano
Unit of Clinical Pharmacology and Pharmacogenetics, Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
Unit of Pneumology, Azienda Ospedaliero-Universitaria Pisana and Department of Translational Research and New Technologies in Medicine, University of Pisa, Pisa, Italy.
Clin Lung Cancer. 2020 May;21(3):232-237. doi: 10.1016/j.cllc.2019.10.003. Epub 2019 Oct 13.
Insights into the mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could provide important information for further patient management, including the choice of second-line treatment. The EGFR T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs. Owing to its biologic relevance in the response of non-small-cell lung cancer (NSCLC) to the selective pressure of treatment, the present study investigated whether the occurrence of T790M at progression differed among patients receiving gefitinib, erlotinib, or afatinib.
The present retrospective study included patients with NSCLC with an EGFR activating mutation, who had received gefitinib, erlotinib, or afatinib as first-line treatment. Plasma samples for the analysis of cell-free DNA were taken at disease progression and analyzed using a digital droplet polymerase chain reaction EGFR mutation assay.
A total of 83 patients were enrolled; 42 had received gefitinib or erlotinib and 41afatinib. The patient characteristics were comparable across the 2 groups. The median time to progression (TTP) was 14.4 months for the gefitinib and erlotinib group and 10.2 months for the afatinib group (P = .09). Of the 83 patients, 47 (56.6%) were positive for the T790M in plasma. A greater incidence of T790M was observed in patients with progression during gefitinib or erlotinib therapy compared with patients treated with afatinib (33 [79%] vs. 14 [34%], respectively; odds ratio, 7.1; 95% confidence interval, 2.7-18.5; P = .0001).
Although gefitinib, erlotinib, and afatinib showed a comparable TTP in patients receiving first-line therapy, the incidence of T790M differed among them, as demonstrated by the present study, which could have implications for the choice of second-line treatment.
深入了解表皮生长因子受体（EGFR）酪氨酸激酶抑制剂（TKIs）的耐药机制可为进一步的患者管理提供重要信息，包括二线治疗的选择。EGFR T790M突变是对第一代和第二代EGFR TKIs耐药的最常见机制。鉴于其在非小细胞肺癌（NSCLC）对治疗选择性压力反应中的生物学相关性，本研究调查了接受吉非替尼、厄洛替尼或阿法替尼治疗的患者在疾病进展时T790M的发生率是否存在差异。
本回顾性研究纳入了具有EGFR激活突变的NSCLC患者，这些患者接受了吉非替尼、厄洛替尼或阿法替尼作为一线治疗。在疾病进展时采集用于分析游离DNA的血浆样本，并使用数字液滴聚合酶链反应EGFR突变检测法进行分析。
共纳入83例患者；42例接受了吉非替尼或厄洛替尼治疗，41例接受了阿法替尼治疗。两组患者的特征具有可比性。吉非替尼和厄洛替尼组的中位疾病进展时间（TTP）为14.4个月，阿法替尼组为10.2个月（P = 0.09）。83例患者中，47例（56.6%）血浆T790M呈阳性。与接受阿法替尼治疗的患者相比，接受吉非替尼或厄洛替尼治疗期间疾病进展的患者中T790M的发生率更高（分别为33例[79%]和14例[34%]；优势比为7.1；95%置信区间为2.7 - 18.5；P = 0.0001）。
尽管吉非替尼、厄洛替尼和阿法替尼在接受一线治疗的患者中显示出相当的TTP，但本研究表明它们之间T790M的发生率存在差异，这可能对二线治疗的选择产生影响。
