IBRANCE(palbociclib,中文药名：帕博西尼[帕布昔利布胶囊])-是十多年来首个获得美国FDA批准的针对ER阳性/HER2阴性绝经后转移性乳腺癌患者的一线治疗新药 IBRANCE(帕博西尼 palbociclib)胶囊 为口服使用 批准日期：2015年2月3日；公司：Pfizer Inc 美国初次批准：2015 适应证和用途 IBRANCE是一个激酶抑制剂适用与来曲唑联用为有雌激素受体(ER)-阳性，人表皮生长因子受体2(HER2)-阴性晚期乳癌绝经后妇女的治疗作为初始基于内分泌治疗对其转移疾病。这个适应证是根据无进展生存(PFS)在加速批准下被批准。剂型批准此适应证可能取决于在验证性试验中临床获益的证明和描述。 剂量和给药方法 IBRANCE胶囊是与食物与来曲唑联用口服。 ⑴推荐开始剂量：125mg每天一次与食物服用共21天接着7天不治疗。 ⑵建议根据个体安全性和耐受性中断和/或剂量减低给药。 药理作用及机制： palbociclib是一种靶向性CDK4/6抑制剂，能够选择性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，阻断肿瘤细胞增殖。 产品特点及优势： Palbociclib为新型分子靶向治疗药物，不良反应能够较好控制和管理，无致癌、致突变、生殖毒性的报道。 Palbociclib联合来曲唑可将乳腺癌患者的中位无疾病生存期（PFS）提高到26.1个月，而单用来曲唑的PFS只有7.5个月。基于这一中期研究结果，2013年4月FDA授予Palbociclib治疗转移性乳腺癌突破性治疗药物。 剂型和规格 胶囊：125mg，100mg和75mg Ibrance 100mg-Kapseln-PFIZER LABORATORIES DIVISION-USA-Vereinigte Staaten von Amerika Ibrance 125mg-Kapseln-PFIZER LABORATORIES DIVISION-USA-Vereinigte Staaten von Amerika Ibrance 75mg-Kapseln-PFIZER LABORATORIES DIVISION-USA-Vereinigte Staaten von Amerika IBRANCE®(palbociclib) is a kinase inhibitor indicated in combination with letrozole for the treatment of postmenopausal women with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer as initial endocrine-based therapy for their metastatic disease. This indication is approved under accelerated approval based on progression-free survival (PFS). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Important Safety Information Neutropenia: Neutropenia is frequently reported with IBRANCE therapy. In the randomized phase II study, Grade 3 (57%) or 4 (5%) decreased neutrophil counts were reported in patients receiving IBRANCE plus letrozole. Febrile neutropenia can occur. Monitor complete blood count prior to starting IBRANCE and at the beginning of each cycle, as well as Day 14 of the first two cycles, and as clinically indicated. For patients who experience Grade 3 neutropenia, consider repeating the complete blood count monitoring 1 week later. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia. Infections: Infections have been reported at a higher rate in patients treated with IBRANCE plus letrozole (55%) compared with letrozole alone (34%). Grade 3 or 4 infections occurred in 5% of patients treated with IBRANCE plus letrozole vs no patients treated with letrozole alone. Monitor patients for signs and symptoms of infection and treat as medically appropriate Pulmonary embolism (PE): PE has been reported at a higher rate in patients treated with IBRANCE plus letrozole (5%) compared with no cases in patients treated with letrozole alone. Monitor patients for signs and symptoms of PE and treat as medically appropriate. Pregnancy and lactation: Based on the mechanism of action, IBRANCE can cause fetal harm. Advise females with reproductive potential to use effective contraception during therapy with IBRANCE and for at least 2 weeks after the last dose. Advise females to contact their healthcare provider if they become pregnant or if pregnancy is suspected during treatment with IBRANCE. Advise women not to breastfeed while on IBRANCE therapy because of the potential for serious adverse reactions in nursing infants from IBRANCE. Additional hematologic abnormalities: Decreases in hemoglobin (83% vs 40%), leukocytes (95% vs 26%), lymphocytes (81% vs 35%), and platelets (61% vs 16%) occurred at a higher rate in patients treated with IBRANCE plus letrozole vs letrozole alone. Adverse reactions: The most common all causality adverse reactions(≥10%) of any grade reported in patients treated with IBRANCE plus letrozole vs letrozole alone in the phase II study included neutropenia (75% vs 5%), leukopenia (43% vs 3%), fatigue (41% vs 23%), anemia (35% vs 7%), upper respiratory infection (31% vs 18%), nausea (25% vs 13%), stomatitis (25% vs 7%), alopecia (22% vs 3%), diarrhea (21% vs 10%), thrombocytopenia (17% vs 1%), decreased appetite (16% vs 7%), vomiting (15% vs 4%), asthenia (13% vs 4%), peripheral neuropathy (13% vs 5%), and epistaxis (11% vs 1%). Grade 3/4 adverse reactions reported(≥10%) occurring at a higher incidence in the IBRANCE plus letrozole vs letrozole alone group include neutropenia (54% vs 1%) and leukopenia (19% vs 0%). The most frequently reported serious adverse events in patients receiving IBRANCE were pulmonary embolism (4%) and diarrhea (2%). General dosing information: The recommended dose of IBRANCE is 125 mg taken orally once daily for 21 days followed by 7 days off treatment in 28-day cycles. IBRANCE should be taken with food and in combination with letrozole 2.5 mg once daily continuously. Patients should be encouraged to take their dose at approximately the same time each day. Capsules should be swallowed whole. No capsule should be ingested if it is broken, cracked, or otherwise not intact. If a patient vomits or misses a dose, an additional dose should not be taken that day. The next prescribed dose should be taken at the usual time. Management of some adverse reactions may require temporary dose interruption/delay and/or dose reduction, or permanent discontinuation. Dose modification of IBRANCE is recommended based on individual safety and tolerability. Drug interactions: Avoid concurrent use of strong CYP3A inhibitors. If patients must be administered a strong CYP3A inhibitor, reduce the IBRANCE dose to 75 mg/day. If the strong inhibitor is discontinued, increase the IBRANCE dose (after 3-5 half-lives of the inhibitor) to the dose used prior to the initiation of the strong CYP3A inhibitor. Grapefruit or grapefruit juice may increase plasma concentrations of IBRANCE and should be avoided. Avoid concomitant use of strong and moderate CYP3A inducers. The dose of the sensitive CYP3A substrates with a narrow therapeutic index may need to be reduced as IBRANCE may increase their exposure. Hepatic and renal impairment: IBRANCE has not been studied in patients with moderate to severe hepatic impairment or in patients with severe renal impairment (CrCl <30 mL/min). https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=86718885-da44-4d3d-b3ca-06cbcedcffd8 乳腺癌突破性治疗药物Ibrance获欧盟批准 2016年11月11日讯  美国制药巨头辉瑞（Pfizer）突破性乳腺癌药物Ibrance（palbociclib）近日在欧盟监管方面传来喜讯。欧盟委员会（EC）已批准Ibrance联合芳香酶抑制剂用于雌激素受体阳性/人类表皮生长因子受体2阴性（（ER+/HER2-）局部晚期或转移性乳腺癌患者的治疗。 此外，Ibrance也已获批联合氟维司群（fulvestrant）用于既往接受过内分泌治疗的ER+/HER2-局部晚期或转移性乳腺癌患者。 Ibrance是欧洲获批的首个CDK4/6抑制剂类抗癌药，该药也是近10年来获批一线治疗ER+/HER2-转移性乳腺癌的首个创新药物，将为欧洲HR+/HER2-转移性乳腺癌患者群体提供一种新的标准护理疗法，并进一步扩大该患者群体的治疗选择。据估计，HER+/HER2-转移性乳腺癌约占转移性乳腺癌病例的60%。 Ibrance的获批，是基于3个随机临床研究的数据。数据显示，与标准的内分泌治疗相比，Ibrance联合内分泌疗法显著延长了HR+/HER2-转移性乳腺癌患者的无进展生存期（PFS）。 关于IBRANCE（palbociclib） Ibrance是一种首创的口服靶向性CDK4/6抑制剂，能够选择性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，阻断肿瘤细胞增殖。细胞周期失控是癌症的一个标志性特征，CDK4/6在许多癌症中均过度活跃，导致细胞增殖失控。CDK4/6是细胞周期的关键调节因子，能够触发细胞周期从生长期（G1期）向DNA复制期（S1期）转变。在雌激素受体阳性（ER+）乳腺癌中，CDK4/6的过度活跃非常频繁，而CDK4/6是ER信号的关键下游靶标。临床前数据表明，CDK4/6和ER信号双重抑制具有协同作用，并能够抑制G1期ER+乳腺癌细胞的生长。