Giordano Pasqualina, Manzo Anna, Montanino Agnese, Costanzo Raffaele, Sandomenico Claudia, Piccirillo Maria Carmela, Daniele Gennaro, Normanno Nicola, Carillio Guido, Rocco Gaetano, Bianco Roberto, Perrone Francesco, Morabito Alessandro
Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy; Clinical Trials Unit, Istituto Nazionale Tumori, "Fondazione G.Pascale" - IRCCS, Napoli, Italy.
Medical Oncology Unit, Thoracic Department, Istituto Nazionale Tumori, "Fondazione G. Pascale" - IRCCS, Napoli, Italy.
Crit Rev Oncol Hematol. 2016 Jan;97:143-51. doi: 10.1016/j.critrevonc.2015.08.016. Epub 2015 Aug 12.
Afatinib is an oral, irreversible, tyrosine kinase inhibitor (TKI) of EGFR, HER2 and HER4. According to phase I studies, the recommended dose of afatinib was 50mg daily. Rash, acne, diarrhea and stomatitis were the most common adverse events. Afatinib failed to demonstrate an improvement in overall survival in unselected heavily pretreated NSCLC patients (Lux-Lung-1). On the contrary, the Lux-Lung-3 and -6 trials met the primary end point, demonstrating a significant increase in terms of PFS with afatinib compared with chemotherapy in the first line treatment of EGFR mutant patients. Moreover, in both studies, afatinib improved overall survival in patients with exon 19 EGFR deletion (31.7 vs 20.7 months; HR: 0.59, p=0.0001). The results of ongoing randomized trials should further clarify the efficacy of afatinib compared with first-generation TKIs in advanced NSCLC, its activity in the adjuvant and neoadjuvant settings, as well as its efficacy in other tumors.
阿法替尼是一种口服的、不可逆的表皮生长因子受体（EGFR）、人表皮生长因子受体2（HER2）和人表皮生长因子受体4（HER4）酪氨酸激酶抑制剂（TKI）。根据I期研究，阿法替尼的推荐剂量为每日50毫克。皮疹、痤疮、腹泻和口腔炎是最常见的不良事件。在未选择的经过大量预处理的非小细胞肺癌（NSCLC）患者中（LUX-Lung-1研究），阿法替尼未能显示出总生存期的改善。相反，LUX-Lung-3和LUX-Lung-6试验达到了主要终点，表明在EGFR突变患者的一线治疗中，与化疗相比，阿法替尼的无进展生存期有显著增加。此外，在这两项研究中，阿法替尼均改善了外显子19 EGFR缺失患者的总生存期（31.7个月对20.7个月；风险比：0.59，p = 0.0001）。正在进行的随机试验结果应能进一步阐明阿法替尼与第一代TKI相比在晚期NSCLC中的疗效、其在辅助和新辅助治疗中的活性以及其在其他肿瘤中的疗效。
