英文药名:Alunbrig(Brigatinib Tablets)
中文药名:布吉他滨片
研发厂家:ARIAD Pharmaceuticals,Inc 药品介绍 新型靶向药brigatinib(商标名 Alunbrig)被FDA加速批准上市 近日,抗癌新药brigatinib(商品名 ALUNBRIG)获得美国食品药品管理局(FDA)的加快核准,用于治疗克唑替尼用药期间进展或无法耐受克唑替尼的间变性淋巴瘤激酶阳性(ALK+)转移性非小细胞肺癌(NSCLC)。该适应证获得加快核准的依据是肿瘤缓解率和缓解持续时间。该适应证的持续核准有待一项证实性试验对临床收益进行验证和描述。ALUNBRIG先前曾获得FDA的突破性治疗药物认证,推荐剂量方案是最初7天90毫克每日一次口服。若最初7天能耐受90毫克,即增至180毫克每日一次口服。可空腹或与食物同服。 批准日期:2017年4月28日 作用机制 Brigatinib是一种酪氨酸激酶抑制剂,其具有针对多种激酶(包括ALK,ROS1,胰岛素样生长因子-1受体(IGF-1R)和FLT-3)以及EGFR缺失和点突变的临床可实现的浓度的体外活性。 Brigatinib在体外和体内测定中抑制ALK的自磷酸化和下游信号蛋白STAT3,AKT,ERK1/2和S6的ALK介导的磷酸化。 Brigatinib还抑制了表达EML4-ALK和NPM-ALK融合蛋白的细胞系的体外增殖,并且证明了小鼠中EML4-ALK阳性NSCLC异种移植物生长的剂量依赖性抑制。 在临床可实现的浓度(≤500nM)下,布吉昔布抑制了表达EML4-ALK的细胞的体外存活力和与ALK抑制剂(包括格列齐特)以及EGFR-Del(E746-A750),ROS1-L2026M ,FLT3-F691L和FLT3-D835Y。 Brigatinib对4种突变形式的EML4-ALK具有体内抗肿瘤活性,包括在crizotinib进展的患者中在NSCLC肿瘤中鉴定的G1202R和L1196M突变体。 Brigatinib还减少了用ALK驱动的肿瘤细胞系颅内注射的小鼠的肿瘤负担和延长的存活。 适用范围及用途 ALUNBRIG是一种激酶抑制剂,用于治疗对间断性淋巴瘤激酶(ALK)阳性转移性非小细胞肺癌(NSCLC)患者的进展,或不耐受crizotinib。该指征根据肿瘤反应率和反应持续时间加快批准。继续批准该指征可能取决于在确认试验中验证和描述临床益处。 剂量和管理 头7天每天口服90毫克;如果耐受,每天口服一次可增加至180毫克。可以带或不带食物。 剂量形式和强度 片剂:30mg和90mg 禁忌症 没有。 警告和注意事项 间质性肺病(ILD)/肺炎:发生在推荐剂量的9.1%患者。监测新的或恶化的呼吸道症状,特别是在治疗的第一周。禁止ALUNBRIG用于新的或恶化的呼吸道症状,并及时评估ILD /肺炎。恢复后,剂量减少或永久停止ALUNBRIG。 高血压:治疗2周后监测血压,然后至少每月治疗。对于严重高血压,禁止ALUNBRIG,然后减少或永久停药。 心动过缓:治疗期间定期监测心率和血压。如果出现症状,禁止使用ALUNBRIG,然后减少或永久停药。 视觉障碍:建议患者报告视觉症状。停止ALUNBRIG并获得眼科评估,然后减少或永久停止ALUNBRIG。 肌酸磷酸激酶(CPK)海拔:在治疗期间定期监测CPK水平。根据严重程度,禁止ALUNBRIG,然后恢复或减少剂量。 胰酶升高:在治疗期间定期监测脂肪酶和淀粉酶水平。根据严重程度,禁止ALUNBRIG,然后恢复或减少剂量。 高血糖症:在开始ALUNBRIG治疗前及时定期评估空腹血清葡萄糖。如果不能通过最佳的医疗管理得到充分的控制,则禁止ALUNBRIG,然后根据严重程度考虑减少剂量或永久停药。 胚胎 - 胎儿毒性:可引起胎儿伤害。向女性提供对胎儿潜在风险的生殖潜力,并使用非激素方法进行有效的避孕。 不良反应 ALUNBRIG最常见的不良反应(≥25%)为恶心,腹泻,疲劳,咳嗽和头痛。 药物相互作用 CYP3A抑制剂:避免与强CYP3A抑制剂同时使用ALUNBRIG。 如果伴随使用强力CYP3A抑制剂是不可避免的,则减少ALUNBRIG的剂量。 CYP3A诱导剂:避免与强CYP3A诱导剂同时使用ALUNBRIG。 CYP3A底物:由于暴露减少,激素避孕药可能无效。 在特定人口中使用 哺乳:建议不要母乳喂养 包装规格/储存与处理 30个毫克片剂:圆形,白色至灰白色的薄膜包衣片剂与凹陷在一侧和滑动在另一侧“U3”;提供: 21片 NDC76189-113-21瓶 180片 NDC76189-113-18瓶 90个毫克片剂:椭圆形,白色至灰白色的薄膜包衣片剂与凹陷在一侧和滑动在另一侧“U7”;提供: 瓶7片 NDC76189-119-07 30片 NDC76189-119-30瓶 商店在控制室温20℃至25℃(68°F至77°F);15℃之间偏移允许至30℃(59°F至86°F)(见USP)。
Alunbrig Granted Accelerated Approval for Metastatic NSCLC The Food and Drug Administration (FDA) has granted accelerated approval to Alunbrig (brigatinib; ARIAD) tablets for the treatment of metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) in patients who have progressed or are intolerant to crizotinib. The accelerated approval was based on data from the ALTA trial, a non-comparative, 2-arm, open-label, multicenter clinical trial showing a clinically meaningful and durable overall response rate (ORR) in patients with locally advanced or metastatic ALK-positive NSCLC who progressed on crizotinib. Study patients were randomized to oral brigatinib 90mg daily (n=112) or brigatinib 180mg daily (n=110) after a 7-day lead-in of 90mg daily. ORR in the 90mg arm was 48% (95% CI: 39%, 58%) and was 53% (95% CI: 43%, 62%) in the 180mg arm. The median duration of responses (DOR) was 13.8 months in both treatment arms. Among patients with measurable brain metastases data, intracranial ORR was 42% (95% IC: 23%, 63%) in the 90mg arm and 67% (95% CI: 41%, 87%) in the 180mg arm. The median intracranial DOR was 5.6 months in the 180mg arm; it was not calculable in the 90mg arm. Moreover, 78% and 68% of patients in the 90mg and 180mg arms who had an intracranial response, respectively, maintained this response for ≥4 months. The most common adverse events (occurring ≥25%) were nausea, diarrhea, fatigue, cough, and headache. The most common serious adverse events were pneumonia and interstitial lung disease (ILD)/pneumonitis. Brigatinib is an investigational oral anaplastic lymphoma kinase (ALK) inhibitor that has activity at clinically achievable concentrations against multiple kinases including ALK, ROS1, insulin-like growth factor-1 receptor (IGF-1R), and FLT-3 as well as EGFR deletion and point mutations. Brigatinib exhibited in vivo anti-tumor activity against four mutant forms of EML4-ALK, including G1202R and L1196M mutants identified in NSCLC tumors in patients who have progressed on crizotinib. Alunbrig will be available as 30mg strength tablets in 21- and 180-count bottles and as 90mg strength tablets in 7- and 30-count bottles. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=07b71b73-1ca3-4e78-a787-e458917f1f23
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