Division of Medical Oncology, Azienda Ospedaliera S Maria della Misericordia, via Dottori, 1, Perugia 06156, Italy.
Expert Rev Anticancer Ther. 2011 May;11(5):673-82. doi: 10.1586/era.11.34.
Epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) represents a distinct disease entity whose molecular phenotype predicts exquisite sensitivity to the reversible EGFR-tyrosine kinase inhibitors (TKIs) gefitinib or erlotinib. However, primary or acquired resistance to these agents remains a major clinical problem. Afatinib is a novel dual irreversible EGFR/HER2 TKI that has been shown in preclinical studies to potentially prevent, delay or overcome resistance to reversible EGFR-TKIs. On this basis, the LUX-Lung clinical trial program has been recently launched for testing this molecule in advanced NSCLC patients. Notably, early results from the randomized LUX-Lung 1 trial indicate that afatinib significantly prolongs progression-free survival compared with placebo in pretreated patients with clinically acquired resistance to gefitinib or erlotinib. On the other hand, the LUX-Lung 2 trial shows that afatinib is highly active in the EGFR-mutant subgroup of patients. While these preliminary data open a new exciting scenario for the future development of anti-EGFR therapies in NSCLC, ongoing afatinib trials will definitively establish a role for this molecule in the treatment of advanced NSCLC.
表皮生长因子受体 (EGFR)-突变非小细胞肺癌 (NSCLC) 是一种独特的疾病实体，其分子表型预示着对可逆 EGFR-酪氨酸激酶抑制剂 (TKI) 吉非替尼或厄洛替尼的高度敏感性。然而，对这些药物的原发性或获得性耐药仍然是一个主要的临床问题。阿法替尼是一种新型的双重不可逆 EGFR/HER2 TKI，在临床前研究中已显示出有可能预防、延迟或克服对可逆 EGFR-TKIs 的耐药性。在此基础上，最近启动了 LUX-Lung 临床试验计划，以测试该分子在晚期 NSCLC 患者中的应用。值得注意的是，随机 LUX-Lung 1 试验的早期结果表明，与安慰剂相比，阿法替尼在对吉非替尼或厄洛替尼获得临床耐药的预处理患者中显著延长了无进展生存期。另一方面，LUX-Lung 2 试验表明，阿法替尼在 EGFR 突变亚组患者中具有高度活性。虽然这些初步数据为 NSCLC 中抗 EGFR 治疗的未来发展开辟了一个令人兴奋的新前景，但正在进行的阿法替尼试验将明确确定该分子在晚期 NSCLC 治疗中的作用。
