2013年7月12日，美国食品药品管理局(FDA)宣布，已批准将Gilotrif(阿法替尼)用于治疗在伴随诊断检测(therascreen EGFR RGQ PCR试剂盒)中发现有表皮生长因子(EGFR)外显子19删除或外显子21 L858R取代基因突变的晚期(转移性)非小细胞肺癌(NSCLC)患者。Gilotrif是一种酪氨酸激酶抑制剂，可阻断促进癌细胞发育的蛋白质。
在一项纳入345例EGFR突变性转移性NSCLC患者的临床研究中，明确了Gilotrif的安全性和有效性。将受试者随机分组，给予Gilotrif或不超过6个周期的培美曲塞加顺铂治疗。结果显示，接受Gilotrif治疗者的无进展生存期较接受化疗者延长了4.2个月。两组总生存期未见统计学差异。
与使用Gilotrif相关的常见不良反应包括腹泻、类似痤疮的皮肤突起、皮肤干燥、瘙痒、口腔炎症、甲沟炎、食欲减退、体重减轻、膀胱炎、鼻衄、鼻溢、发热、眼部炎症和低钾血症。严重不良反应包括可导致肾衰竭和重度脱水的腹泻、重度皮疹、肺部炎症和肝脏毒性。

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Diarrhea

Diarrhea has resulted in dehydration with or without renal impairment; some of these cases were fatal. In the pivotal study, diarrhea occurred in 96% of patients treated with GILOTRIF (n=229), of which 15% was Grade 3 in severity and occurred within the first 6 weeks. Renal impairment as a consequence of diarrhea occurred in 6.1% of patients treated with GILOTRIF, out of which 3 (1.3%) were Grade 3.

For patients who develop prolonged Grade 2 diarrhea lasting more than 48 hours or greater than or equal to Grade 3 diarrhea, withhold GILOTRIF until diarrhea resolves to Grade 1 or less, and resume GILOTRIF with appropriate dose reduction. Provide patients with an anti-diarrheal agent (e.g., loperamide) for self-administration at the onset of diarrhea and instruct patients to continue anti-diarrheal therapy until loose bowel movements cease for 12 hours.

Bullous and Exfoliative Skin Disorders

Grade 3 cutaneous reactions characterized by bullous, blistering, and exfoliating lesions occurred in 6 (0.15%) of the 3865 patients who received GILOTRIF across clinical trials. In the pivotal study, the overall incidence of cutaneous reactions consisting of rash, erythema, and acneiform rash was 90%, and the incidence of Grade 3 cutaneous reactions was 16%. In addition, the incidence of Grade 1-3 palmar-plantar erythrodysesthesia syndrome was 7%. Discontinue GILOTRIF in patients who develop life-threatening bullous, blistering, or exfoliating lesions. For patients who develop prolonged Grade 2 cutaneous adverse reactions lasting more than 7 days, intolerable Grade 2, or Grade 3 cutaneous reactions, withhold GILOTRIF until the adverse reaction resolves to Grade 1 or less, and resume GILOTRIF with appropriate dose reduction.

Interstitial Lung Disease (ILD)

ILD or ILD-like adverse reactions (e.g., lung infiltration, pneumonitis, acute respiratory distress syndrome, or alveolitis allergic) occurred in 1.5% of the 3865 patients who received GILOTRIF across clinical trials; of these, 0.4% were fatal. The incidence of ILD appeared to be higher in patients of Asian ethnicity (2.1%) as compared to non-Asians (1.2%). In the pivotal study, the incidence of Grade ≥3 ILD was 1.3% and resulted in death in 1% of GILOTRIF-treated patients.

Withhold GILOTRIF during eva luation of patients with suspected ILD, and discontinue GILOTRIF in patients with confirmed ILD.

Hepatic Toxicity

In 3865 patients who received GILOTRIF across clinical trials, 10.1% had liver test abnormalities, of which 7 (0.18%) were fatal.  In the pivotal study, liver test abnormalities of any grade occurred in 17.5% of the patients treated with GILOTRIF.

Obtain periodic liver testing in patients during treatment with GILOTRIF. Withhold GILOTRIF in patients who develop worsening of liver function. In patients who develop severe hepatic impairment whi