阿贝西利Verzenio 100mg Tablets(abemaciclib)

药店国别： 产地国家：美国 处方药：是 所属类别： 100毫克/片 14片/盒 包装规格： 100毫克/片 14片/盒 计价单位：盒 生产厂家中文参考译名： 生产厂家英文名：Eli Lilly 原产地英文商品名：Verzenio 100mg/Tablets 14Tablets/box 原产地英文药品名：abemaciclib 中文参考商品译名：Verzenio片 100毫克/片 14片/盒 中文参考药品译名：abemaciclib 曾用名： 简介： 晚期乳腺癌新靶向药Verzenio 又给患者增添新的生命希望近日，乳腺癌新药Abemaciclib(商品名：Verzenio)获FDA批准上市，其产品既可单独使用治疗化疗/内分泌疗法后转移性乳腺癌，也可与氟维司群联用治疗HR+/HER2-的晚期或转移性乳腺癌患者。Verzenio是美国FDA批准的第三款CDK4/6抑制剂，也是唯一一款获批作为单独疗法使用的CDK4/6抑制剂。CDK4/6抑制剂是通过选择性地抑制细胞周期蛋白依赖性激酶4和6(CDK4/6)，恢复细胞周期控制，从而起到阻断肿瘤细胞增殖的作用。批准日期：2017年9月28日 公司：Eli Lilly公司VERZENIO(abemaciclib)片剂，用于口服美国最初批准：2017年 作用机制 Abemaciclib是细胞周期蛋白依赖性激酶4和6(CDK4和CDK6)的抑制剂。这些激酶在与D-细胞周期蛋白结合后被激活。 在雌激素受体阳性(ER +)乳腺癌细胞系中，细胞周期蛋白D1和CDK4 / 6促进视网膜母细胞瘤蛋白(Rb)的磷酸化，细胞周期进程和细胞增殖。 在体外，持续暴露于abemaciclib可抑制Rb磷酸化并阻止细胞周期从G1期进入S期，从而导致衰老和凋亡。 在乳腺癌异种移植模型中，作为单一药剂或与抗雌激素药组合每日不间断给药的abemaciclib导致肿瘤尺寸减小。 适应症和用法 VERZENIO™是一种激酶抑制剂，表明：结合芳香酶抑制剂作为初始内分泌治疗，用于治疗绝经后妇女的激素受体(HR)阳性，人表皮生长因子受体2(HER2)阴性晚期或转移性乳腺癌。与氟维司群联合用于治疗患有激素受体(HR)阳性，人表皮生长因子受体2(HER2)阴性晚期或转移性乳腺癌的女性，其在内分泌治疗后具有疾病进展。作为单一疗法用于治疗患有HR阳性，HER2阴性晚期或转移性乳腺癌的成人患者，其在内分泌治疗和转移性环境中的先前化疗后具有疾病进展。 剂量和给药 VERZENIO片剂在有或没有食物的情况下口服。推荐的起始剂量与氟维司群或芳香酶抑制剂组合：150mg，每日两次。单药治疗的推荐起始剂量：每日两次200毫克。基于个体安全性和耐受性，可能需要剂量中断和/或剂量减少。剂量形式和强度片剂：50mg，100mg，150mg和200mg。 禁忌症 没有。 警告和注意事项 腹泻：指导患者在第一次出现稀便迹象时开始进行止泻治疗，增加口服液，并通知其医务人员。中性粒细胞减少症：监测VERZENIO治疗开始前的全血细胞计数，前2个月每2周一次，接下来2个月每月一次，临床指征。肝毒性：已观察到血清转氨酶水平升高。在开始使用VERZENIO治疗前进行肝功能检查(LFT)。前两个月每两周监测一次LFT，接下来的两个月监测LFT，并按临床指示。静脉血栓栓塞：监​​测患者血栓形成和肺栓塞的症状和体征，并视为医学上适当的。胚胎 - 胎儿毒性：可能导致胎儿伤害。告知患有胎儿潜在风险并使用有效避孕措施的患者。 不良反应 最常见的不良反应(发生率≥20%)是腹泻，中性粒细胞减少，恶心，腹痛，感染，疲劳，贫血，白细胞减少，食欲减退，呕吐，头痛，脱发和血小板减少。 药物相互作用 CYP3A抑制剂：避免同时使用酮康唑。减少VERZENIO剂量，同时使用其他强效CYP3A抑制剂。CYP3A诱导剂：避免同时使用强CYP3A诱导剂。 用于特定人群哺乳期： 建议不要母乳喂养。包 装提供/存储和处理 提供VERZENIO 50毫克片剂是椭圆形米色片剂，一面是“Lilly”，另一面是“50”。VERZENIO 100毫克片剂是椭圆形白色至几乎是白色片剂，一侧是“Lilly”，另一侧是“100”。VERZENIO 150毫克片剂是椭圆形黄色片剂，一侧是“Lilly”，另一侧是“150”。VERZENIO 200毫克片剂是椭圆形米色片剂，一面是“Lilly”，另一面是“200”。VERZENIO片剂以7天剂量包装配置提供如下：200毫克剂量包装(14片) - 每个泡罩包装含有14片(每片200毫克)(200毫克，每天两次)NDC 0002-6216-54150毫克剂量包(14片) - 每个泡罩包装含14片(每片150毫克)(150毫克，每天两次)NDC 0002-5337-54100毫克剂量包(14片) - 每个泡罩包装含14片(每片100毫克)(100毫克，每天两次)NDC 0002-4815-5450毫克剂量包(14片) - 每个泡罩包装含14片(每片50毫克)(50毫克，每天两次)NDC 0002-4483-54 存储和处理 储存在20°C至25°C(68°F至77°F);允许的偏差为15°C至30°C(59°F至86°F)。 英文版说明书 Approves Abemaciclib for HR+/HER2- Breast CancerThe FDA approved abemaciclib (Verzenio) for use in combination with fulvestrant in women with HR+/HER2- advanced breast cancer with disease progression following endocrine therapy. The CDK4/6 inhibitor has also been approved as a monotherapy for patients with HR+/HER2- breast cancer with metastatic disease who have previously received endocrine therapy and chemotherapy.Support for the combination indication comes from the phase III MONARCH 2 trial, in which adding abemaciclib to fulvestrant reduced the risk of disease progression or death by 45% versus fulvestrant alone.1 The single-agent approval is based on the single-arm phase II MONARCH 1 trial, in which the median progression-free survival (PFS) in this patient population was 6 months (95% CI 4.2-7.5) and the median overall survival (OS) was 17.7 months (95% CI, 16 to not reached)."Verzenio provides a new targeted treatment option for certain patients with breast cancer who are not responding to treatment, and unlike other drugs in the class, it can be given as a stand-alone treatment to patients who were previously treated with endocrine therapy and chemotherapy," Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence and acting director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug eva luation and Research, said in a statement.In the international, double-blind phase III MONARCH 2 trial, 669 patients were randomized in a 2:1 ratio to abemaciclib plus fulvestrant (n = 446) or fulvestrant plus placebo (n = 223). Patients had progressed during neoadjuvant or adjuvant endocrine therapy, within 12 months of adjuvant endocrine therapy, or during frontline endocrine treatment for metastatic disease. Individuals were excluded from enrollment if they were administered chemotherapy or more than 1 endocrine therapy in the metastatic setting.Patient characteristics were well-balanced between the 2 arms. Overall, 82% of patients were postmenopausal, 72% had measurable disease, 56% had visceral disease, and 25% had primary endocrine therapy resistance. About 60% of patients had received chemotherapy in the adjuvant or neoadjuvant setting.Patients received 500 mg (per label) of fulvestrant plus placebo or 150 mg of abemaciclib twice daily. The initial abemaciclib dose was 200 mg twice daily; however, the dose was amended after the first 178 patients were enrolled, due to diarrhea-related toxicity concerns. A GnRH agonist was given to pre/perimenopausal patients. The primary endpoint for the trial was PFS. Secondary endpoints included OS, response, clinical benefit rate, and safety.Following 379 PFS events in the intent-to-treat population, the median PFS was 16.4 months in the abemaciclib arm versus 9.3 months in the fulvestrant-alone group (HR, 0.553; 95% CI, 0.449-0.681; P <.0000001). The overall response rates (ORRs) among patients with measurable disease were 48.1% and 21.3% in the abemaciclib and control arms, respectively.The 48.1% ORR in the abemaciclib cohort included a complete response rate of 3.5%. There were no complete responses in the control arm. The median duration of response was 25.6 months in the placebo arm and had not yet been reached in the fulvestrant arm. The OS data are not yet mature.The most common all-grade treatment-related adverse events (AEs) with the abemaciclib combination versus fulvestrant alone were diarrhea (86.4% vs 24.7%), neutropenia (46.0% vs 4.0%), nausea (45.1% vs 22.9%), and fatigue (39.9% vs 26.9%).The most frequently reported grade 3 AEs in the abemaciclib versus fulvestrant-alone arms were neutropenia (23.6% vs 1.3%) and diarrhea (13.4% vs 0.4%). Grade 4 neutropenia occurred in 2.9% versus 0.4% of the abemaciclib and fulvestrant-alone groups, respectively. There were 3 deaths in the abemaciclib arm linked to treatment-related AEs, compared with none in the control arm.The MONARCH 1 trial included 132 patients with HR+/HER2- metastatic breast cancer who progressed during or after endocrine therapy and chemotherapy. The median age was 58 years (range, 36-89), 44.7% of patients had an ECOG performance status of 1, 90.2% had visceral disease, and 85.6% had at least 2 metastatic sites. Patients with CNS metastases were excluded from enrollment.Patients had received a median of 3 (range, 1-8) prior lines of therapy—including a median of 2 lines of chemotherapy—for metastatic disease. Sixty-seven patients (50.8%) had received fulvestrant in the metastatic setting. With chemotherapy, 68.9% (n = 91) of patients had received a taxane and 55.3 % (n = 73) of patients had received capecitabine in the metastatic setting.Abemaciclib was administered at 200 mg orally every 12 hours on a continuous schedule until progression or unacceptable toxicity. At the 8-month interim analysis, 35.6% of patients had received at least 8 cycles of the CDK4/6 inhibitor.ORR was the primary outcome measure. Secondary endpoints included duration of response, PFS, OS, clinical benefit rate, and safety.The investigator-assessed, confirmed ORR was 19.7% (n = 26; 95% CI, 13.3-27.5), which included all partial responses (PR). The rate of patients with stable disease (SD) ≥6 months was 22.7%, leading to a clinical benefit rate (complete response + PR + SD ≥6 months) of 42.4%. The median time to response was 3.7 months and the median duration of response was 8.6 months. Thirty-four patients had progressive disease.The most common non-laboratory, all-grade AEs were diarrhea (90.2%), fatigue (65.2%), nausea (64.4%), decreased appetite (45.5%), and abdominal pain (38.6%). The grade 3 rates of these events were 19.7% for diarrhea, 12.9% for fatigue, 4.5% for nausea, 3.0% for decreased appetite, and 2.3% for abdominal pain.Leukopenia (27.4%) and neutropenia (22.3%) were the most common laboratory AEs. The only grade 4 AE of any kind in the trial was neutropenia, which occurred in 4.6% of patients.Serious AEs occurred in 24.2% (n = 32) of patients, with AEs leading to treatment discontinuation in 7.6% (n = 10) of patients. Dose reductions were required for 49.2% of patients (n = 65). The most common reason for dose reductions were diarrhea (20.5%) and neutropenia (10.6%). There were 2 patient deaths during treatment and 1 patient death within 30 days after study discontinuation.