Medical Oncology Unit of Respiratory Tract & Sarcomas, New Drugs Development Division, European Institute of Oncology, Milan, Italy.
Future Oncol. 2013 Mar;9(3):327-45. doi: 10.2217/fon.13.6.
Erlotinib is an orally administered small-molecule inhibitor of EGF receptor (EGFR) tyrosine kinase that is approved for the treatment of non-small-cell lung cancer (NSCLC) and pancreatic cancer. Erlotinib was first approved for the treatment of unselected NSCLC patients with advanced disease after failure of at least one prior chemotherapy regimen, and it was subsequently demonstrated to also confer a significant clinical benefit as maintenance therapy after first-line platinum-based chemotherapy. In all clinical studies, erlotinib treatment was associated with a good safety profile. Activating mutations in the EGFR gene have emerged as the strongest predictive marker of response to tyrosine kinase inhibitors, erlotinib and gefitinib, independently of other clinical and molecular features. Results from recently published, randomized Phase III trials showed that first-line erlotinib significantly prolongs progression-free survival in patients with advanced EGFR mutation-positive NSCLC with favorable tolerability, compared with standard chemotherapy. EGFR mutation testing is a crucial factor in the decision-making process regarding the most appropriate initial treatment option for patients. Specific molecular alterations in crucial genes have been discovered and associated with resistance to erlotinib, limiting its efficacy. New targeted agents and combined-treatment strategies are now under evaluation in clinical trials of NSCLC patients following progression to tyrosine kinase inhibitors.
厄洛替尼是一种口服小分子表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，已被批准用于治疗非小细胞肺癌（NSCLC）和胰腺癌。厄洛替尼最初被批准用于治疗至少一种一线化疗方案失败后的晚期非小细胞肺癌患者，随后的研究表明，它作为一线铂类化疗后的维持治疗也能显著提高临床获益。在所有的临床研究中，厄洛替尼治疗的安全性良好。EGFR 基因的激活突变已成为对酪氨酸激酶抑制剂厄洛替尼和吉非替尼反应的最强预测标志物，独立于其他临床和分子特征。最近发表的随机 III 期临床试验结果表明，一线厄洛替尼治疗与标准化疗相比，显著延长了晚期 EGFR 突变阳性 NSCLC 患者的无进展生存期，且耐受性良好。EGFR 基因突变检测是决定患者初始治疗方案的关键因素。在关键基因中发现了特定的分子改变，并与厄洛替尼耐药相关，限制了其疗效。在酪氨酸激酶抑制剂进展后的 NSCLC 患者的临床试验中，新的靶向药物和联合治疗策略正在评估中。
