新型抗癌口服药Alectinib Capsule(Alecensa/AP26113)为新一代的双重抑制剂，突破性治疗转移非小细胞肺癌
近日，美国FDA批准阿雷替尼胶囊Alecensa（alectinib）用于治疗晚期（转移性）ALK 阳性非小细胞肺癌，适用于经另一种治疗药物-克唑替尼治疗后恶化或不对其耐受的患者。
FDA的药品评价和研究中心中血液学和肿瘤学主任说：“今天的批准为一组患者一旦他们的疾病用Xalkori治疗不再响应提供一种新治疗选择，” “Alecensa临床试验提供证据除了对在肺中肿瘤主要作用外，对已播散至脑肿瘤作用，这是对临床医生要了解的重要效应。” 加快审批，突破性治疗指定，优先审评状态和孤儿药物指定
批准日前：2015年12月11日：公司：Genentech
ALECENSA(阿雷替尼 alectinib)胶囊，供口服使用
美国初次批准：2015
作用机制
Alectinib是一种酪氨酸激酶抑制剂靶向ALK和RET。在非临床研究，alectinib抑制ALK 磷酸化和ALK-介导的下游信号蛋白STAT3和AKT的激活，和在窝藏ALK 融合，扩增，或激活突变多种细胞系减低肿瘤细胞活力。Alectinib的主要活性代谢物，M4，显示相似体外效力和活性。Alectinib和M4显示体外和体内对多种ALK 酶突变型，包括有些用克里唑蒂尼已进展患者NSCLC肿瘤内鉴定的突变体，在移植携带ALK融合肿瘤的小鼠模型中，给予alectinib 导致抗肿瘤活性和延长生命，包括颅内植入来自有ALK-肿瘤细胞系小鼠模型。
适应证和用途
ALECENSA是一个激酶抑制剂适用为的治疗有间变性淋巴瘤激酶(ALK)-阳性，转移非小细胞肺癌(NSCLC)进展对或是对克里唑蒂尼耐受的患者的治疗。这个适应证是在加快审批下被批准根据肿瘤反应率和反应时间。继续批准这个适应证可能取决于在验证性试验中临床获益的验证和描述。
剂量和给药方法
600mg口服每天2次。与食物给予ALECENSA。
剂型和规格
胶囊：150mg
禁忌证
无。
警告和注意事项
⑴ 肝毒性：监视肝实验室测试每2周治疗的头2个月期间，和任何治疗期间定期。严重ALT，AST，或胆红素升高情况中，不给，然后减低剂量，或永久地终止ALECENSA。
⑵间质性肺病(ILD)/肺炎：0.4%患者发生。被诊断ILD/肺炎患者立即不给ALECENSA和如已确定没有ILD/肺炎的其他潜在原因永久地终止。
⑶心动过缓：常规地监视心率和血压。如症状性，不给ALECENSA然后减低剂量，或永久地终止。
⑷严重肌痛和肌酸磷酸激酶(CPK)升高：发生分别在1.2%和4.6%患者。治疗的头一个月期间每2周评估CPK和在患者报告不解释肌痛，触痛，或乏力。在严重CPK升高情况中，不给，然后恢复或减低剂量。
⑸胚胎胎儿毒性：ALECENSA可能致胎儿危害。忠告有生殖潜能女性对胎儿潜在风险和使用有效避孕。
不良反应
最常见不良反应(发生率≥20%)是疲乏，便秘，水肿和肌痛。
特殊人群中使用
哺乳：不要哺乳喂养。
如何供应/贮存和处置
硬胶囊，白色150mg胶囊在帽上黑墨汁印有“ALE”和体上印有“150mg”，可得到以下：
240胶囊每瓶：NDC 50242-130-01
贮存和稳定性：不要贮存30°C(86°F)以上。贮存在原始容器避光和潮湿保护

Alecensa approval provides new therapy for lung cancer
ALECENSA is indicated for the treatment of patients with anaplastic lymphoma kinase (ALK)-positive, metastatic non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.
This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.
Important Safety Information
Warnings and Precautions
Hepatotoxicity
•Elevations of AST >5X the upper limit of normal (ULN) occurred in 3.6% of patients, and elevations of ALT >5X the ULN occurred in 4.8% of patients. Elevations of bilirubin >3X the ULN occurred in 2.8% of patients. The majority (73% of the patients with hepatic transaminase elevations and 49% of the patients with bilirubin elevations) of these events occurred during the first 2 months of treatment. Four patients discontinued ALECENSA for Grade 3-4 AST and/or ALT elevations, and three patients discontinued ALECENSA for Grade 3 bilirubin elevations. Two patients with Grade 3-4 AST/ALT elevations had documented drug-induced liver injury by liver biopsy
•Monitor liver function tests including ALT, AST, and total bilirubin every 2 weeks during the first 2 months of treatment, then periodically during treatment, with more frequent testing in patients who develop transaminase and bilirubin elevations. Based on the severity of the adverse drug reaction, withhold ALECENSA and resume at a reduced dose, or permanently discontinue ALECENSA
Interstitial Lung Disease (ILD)/Pneumonitis
•Severe ILD (Grade 3) occurred in one (0.4%) of 253 patients exposed to ALECENSA in clinical trials
•Promptly investigate for ILD/pneumonitis in any patient who presents with worsening of respiratory symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, and fever)
•Immediately withhold ALECENSA treatment in patients diagnosed with ILD/pneumonitis and permanently discontinue ALECENSA if no other potential causes of ILD/pneumonitis have been identified
Bradycardia
•Symptomatic bradycardia can occur with ALECENSA. Cases of bradycardia (7.5%) have been reported in patients treated with ALECENSA. Twenty percent of 221 patients treated with ALECENSA for whom serial ECGs were available had heart rates of
•Monitor heart rate and blood pressure regularly. If symptomatic, withhold ALECENSA then dose reduce or permanently discontinue
•Permanently discontinue ALECENSA in cases of life-threatening bradycardia if no contributing concomitant medication is identified
Severe Myalgia and Creatine Phosphokinase (CPK) Elevation
•Myalgia or musculoskeletal pain occurred in 29% of patients in clinical trials. The incidence of Grade 3 myalgia/musculoskeletal pain was 1.2%. Dose modifications for myalgia/musculoskeletal pain were required in 0.8% of patients
•Elevations of CPK occurred in 43% of 218 patients with CPK laboratory data available in clinical trials. The incidence of Grade 3 elevations of CPK was 4.6%. Median time to Grade 3 CPK elevation was 14 days (interquartile range 13-14 days). Dose modifications for elevation of CPK occurred in 5.0% of patients
•Advise patients to report any unexplained muscle pain, tenderness, or weakness. Assess CPK levels every 2 weeks for the first month of treatment and as clinically indicated in patients reporting symptoms. Based on the severity of the CPK elevation, withhold, then resume or dose reduce ALECENSA
Embryo-Fetal Toxicity
•ALECENSA can cause fetal harm when administered to pregnant women. Administration of ALECENSA to pregnant rats and rabbits during the period of organogenesis resulted in embryo-fetal toxicity and abortion at maternally toxic doses with exposures approximately 2.7X those observed in humans with ALECENSA 600 mg twice daily. Advise pregnant women of the potential risk to a fetus
•Advise females of reproductive potential to use effective contraception during treatment with ALECENSA and for 1 week following the final dose
Most Common Adverse Reactions
•The most common adverse reactions (incidence ≥20%) were fatigue, constipation, edema, and myalgia. Management of adverse events may require temporary interruption, dose reduction, or discontinuation of treatment with ALECENSA
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