Mazza Valentina, Cappuzzo Federico
Department of Oncology-Hematology.
Department of Medical Oncology, AUSL Romagna, Ravenna, Italy.
Appl Clin Genet. 2017 Jul 26;10:49-56. doi: 10.2147/TACG.S103471. eCollection 2017.
The discovery of mutations in significantly changed the treatment paradigm of patients with -mutant non-small cell lung cancer (NSCLC), a particular group of patients with different clinical characteristics and outcome to -wild-type patients. In these patients, the treatment of choice as first-line therapy is first- or second-generation EGFR-tyrosine kinase inhibitors (EGFR-TKIs), such as gefitinib, erlotinib, or afatinib. Inevitably, after the initial response, all patients become refractory to these drugs. The most common mechanism of acquired resistance to EGFR-TKIs is the development of a second mutation in exon 20 of (). Osimertinib is a third-generation EGFR-TKI designed for overcoming -mediated resistance. Based on the results of efficacy and tolerability of Phase II and Phase III studies, osimertinib has been approved for treatment of advanced mutation NSCLC following progression on a prior EGFR-TKI. Occurrence of acquired resistance to osimertinib represents an urgent need for additional strategies including combination with other agents, such as other targeted therapies or checkpoint inhibitors, or development of new and more potent compounds.
在 中发现的突变显著改变了携带 突变的非小细胞肺癌（NSCLC）患者的治疗模式，这是一组具有不同临床特征且预后与 野生型患者不同的特定患者群体。在这些患者中，作为一线治疗的首选是第一代或第二代表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs），如吉非替尼、厄洛替尼或阿法替尼。不可避免的是，在初始反应后，所有患者都会对这些药物产生耐药性。对EGFR-TKIs获得性耐药的最常见机制是 在第20外显子发生第二次突变。奥希替尼是一种旨在克服 介导的耐药性的第三代EGFR-TKI。基于II期和III期研究的疗效和耐受性结果，奥希替尼已被批准用于治疗在先前EGFR-TKI治疗后进展的晚期 突变NSCLC。对奥希替尼产生获得性耐药的情况迫切需要其他策略，包括与其他药物联合使用，如其他靶向治疗或检查点抑制剂，或开发新的、更有效的化合物。
