Passaro Antonio, Guerini-Rocco Elena, Pochesci Alessia, Vacirca Davide, Spitaleri Gianluca, Catania Chiara Matilde, Rappa Alessandra, Barberis Massimo, de Marinis Filippo
Division of Thoracic Oncology, European Institute of Oncology, Milan, Italy.
Clinic Unit of Histopathology and Molecular Diagnostics, Division of Pathology, European Institute of Oncology, Milan, Italy.
Pharmacol Res. 2017 Mar;117:406-415. doi: 10.1016/j.phrs.2017.01.003. Epub 2017 Jan 12.
The identification of EGFR mutations and their respectively tyrosine kinase inhibitors (TKIs), changed dramatically treatment and survival of patients with EGFR-positive lung cancer. Nowadays, different EGFR TKIs as afatinib, erlotinib and gefitinib are approved worldwide for the treatment of NSCLC harbouring EGFR mutations, in particular exon 19 deletions or exon 21 (Leu858Arg) substitution EGFR mutations. In first-line setting, when comparing with platinum-based chemotherapy, these target drugs improves progression-free survival, response rate and quality of life. Unfortunately, the development of different mechanism of resistance, limits the long term efficacy of these agents. The most clear mechanism of resistance is the development of EGFR Thr790Met mutation. Against this new target, different third-generation EGFR-mutant-selective TKIs, such as osimertinib, rociletinib and olmutinib, showed a great activity. In this review, we summarize the scientific evidences about biology, evaluation and treatment on NSCLC with EGFR T790M mutation.
表皮生长因子受体（EGFR）突变及其相应的酪氨酸激酶抑制剂（TKIs）的发现，极大地改变了EGFR阳性肺癌患者的治疗方式和生存期。如今，不同的EGFR TKIs，如阿法替尼、厄洛替尼和吉非替尼，在全球范围内被批准用于治疗携带EGFR突变的非小细胞肺癌（NSCLC），特别是外显子19缺失或外显子21（Leu858Arg）替代的EGFR突变。在一线治疗中，与铂类化疗相比，这些靶向药物可提高无进展生存期、缓解率和生活质量。不幸的是，不同耐药机制的出现限制了这些药物的长期疗效。最明确的耐药机制是EGFR Thr790Met突变的发生。针对这一新靶点，不同的第三代EGFR突变选择性TKIs，如奥希替尼、罗西替尼和奥美替尼，显示出强大的活性。在本综述中，我们总结了关于EGFR T790M突变NSCLC的生物学、评估和治疗的科学证据。
