ZYKADIA(ceritinib/LDK378,色瑞替尼）为新一代非小细胞肺癌口服药
2015年3月2日,欧洲药品管理局（EMA）人用医药产品委员会（CHMP）已建议批准Zykadia，用于经ALK抑制剂Xalkori（crizotinib，克唑替尼）治疗后病情恶化的间变性淋巴瘤激酶阳性（ALK+）转移性非小细胞肺癌（NSCLC）成人患者的治疗。如果获批，Zykadia将成为欧洲Xalkori经治ALK+NSCLC患者的首个治疗方案，将解决这一群体中远未满足的医疗需求。欧盟委员会（EC）在做出最终审查决定时，通常都会采纳CHMP的建议。这意味着，Zykadia将在未来3个月内获批上市，这也标志着Zykadia继美国FDA批准之后的又一个监管里程碑。
在全球范围内，肺癌是癌症死亡的主要病因之一，据估计每年有160万人确诊肺癌。非小细胞肺癌（NSCLC）是最常见类型，约占所有病例的85-90%，其中2-7%病例由ALK基因重排驱动，导致癌细胞加速生长。Xalkori是由辉瑞研发的全球首个间变性淋巴瘤激酶（ALK）靶向治疗药物，该药的上市极大地改变了晚期ALK+NSCLC患者的临床治疗，但病情恶化往往不可避免，当肿瘤对Xalkori无响应后，患者鲜有治疗方案，Zykadia将成为这一群体的重要治疗选择。
CHMP的积极建议，是基于2项全球性多中心开放标签单组研究（Study A和Study B）的数据。Study A是一项I期研究，包括一个剂量递增阶段和一个扩展阶段（推荐剂量750mg）。该研究在246例ALK+NSCLC患者中开展，其中163例既往接受过一种ALK抑制剂（Xalkori）治疗，另外83例为ALK抑制剂初治。数据显示，Xalkori经治组（n=163），总缓解率（ORR）为56.4%（95%CI，48.5-64.2%），中位缓解持续时间（DOR）为8.3个月（95%CI,6.8-9.7个月），中位无进展生存期（PFS）为6.9个月（95%CI,5.6-8.7个月）。Study B研究是一项II期研究，评估了750mg剂量Zykadia治疗局部晚期或转移性ALK+NSCLC的疗效和安全性，涉及140例既往经1-3线化疗后接受crizotinib治疗病情恶化的患者。
关于Zykadia
Zykadia是一种口服、选择性间变性淋巴瘤激酶（ALK）抑制剂。在肺癌的临床治疗中，ALK是一个重要的治疗靶标。ALK基因能够与其他基因融合，表达一种异常的融合蛋白，促进癌细胞的形成和生长。
Zykadia目前已被批准在美国，墨西哥，智利，韩国，危地马拉和厄瓜多尔治疗成年患者的ALK +非小细胞肺癌。额外的监管审查正在中北美，南美，中美洲和亚洲进行。在欧盟，Zykadia（ceritinib）是一种试验药物并没有被监管机构批准。

IMPORTANT SAFETY INFORMATION ABOUT ZYKADIA™ (ceritinib) CAPSULES AND INDICATION

IMPORTANT SAFETY INFORMATION AND INDICATION
ZYKADIA may cause serious side effects, such as:
Stomach and intestinal problems
ZYKADIA causes stomach and intestinal problems in most people, including diarrhea, nausea, vomiting, and stomach-area pain. These problems can sometimes be severe. Follow your health care provider's instructions about taking medicines to help these symptoms. Call your health care provider for advice if your symptoms are severe or do not go away
Liver problems
ZYKADIA may cause liver injury. Your health care provider should do blood tests at least every month to check your liver while you are taking ZYKADIA. Tell your doctor right away if you experience any of the following symptoms:
Tiredness (fatigue)
Yellowing of skin or the whites of eyes
Decreased appetite
Urine turns dark or brown
Itchy skin
Nausea or vomiting
Pain on the right side of your stomach
Bleed or bruise more easily than normal
Lung problems (pneumonitis)
ZYKADIA may cause severe or life-threatening swelling (inflammation) of the lungs during treatment that can lead to death. Symptoms may be similar to those symptoms from lung cancer. Tell your doctor right away if you have any new or worsening symptoms, including:
Trouble breathing or shortness of breath
Cough, with or without mucous
Fever
Chest pain
Heart problems
ZYKADIA may cause very slow, very fast, or abnormal heartbeats. Your health care provider may check your heart during treatment with ZYKADIA. Tell your health care provider right away if you feel new chest pain or discomfort, dizziness or lightheadedness, faint, or have abnormal heartbeats. Tell your health care provider if you start to take or have any changes in heart or blood pressure medicines
High blood sugar (hyperglycemia)
People who have diabetes or glucose intolerance, or who take a corticosteroid medicine have an increased risk of high blood sugar with ZYKADIA. Follow your health care provider's instructions about monitoring your blood sugar. Call your health care provider right away if you have any symptoms of high blood sugar, including:
Increased thirst
Urinating often
Increased hunger
Blurred vision
Headaches
Tiredness
Trouble thinking or concentrating
Your breath smells like fruit
Before you take ZYKADIA, tell your doctor about all of your medical conditions, including if you:
Have liver problems
Have diabetes or high blood sugar
Have heart problems, including a condition called long QT syndrome
Are pregnant, think you may be pregnant, or plan to become pregnant. ZYKADIA may harm your unborn baby
Women who are able to become pregnant must use an effective method of birth control during treatment with ZYKADIA and for at least 2 weeks after stopping ZYKADIA. Talk to your health care provider about birth control methods that may be right for you
Are breastfeeding or plan to breastfeed
It is not known if ZYKADIA passes into your breast milk. You should not breastfeed if you take ZYKADIA.
It is not known if ZYKADIA passes into your breast milk. You should not breastfeed if you take ZYKADIA.
Tell your doctor about the medicines you take, including:
Prescription medicines
Vitamins
Over-the-counter medicines
Herbal supplements
The most common side effects of ZYKADIA include:
Diarrhea
Stomach-area pain
Constipation
Nausea
Tiredness (fatigue)
Vomiting
Decreased appetite
Tell your doctor if you have any side effect that bothers you or does not go away. These are not all of the possible side effects of ZYKADIA. For more information, ask your doctor or pharmacist. You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
How to take ZYKADIA and what to avoid
Take ZYKADIA exactly as your health care provider tells you. Do not change your dose or stop taking unless your health care provider tells you to
Take ZYKADIA 1 time each day
Take ZYKADIA on an empty stomach, do not eat for 2 hours before and do not eat for 2 hours after taking ZYKADIA
If you miss a dose of ZYKADIA, take it as soon as you remember. If your next dose is due within 12 hours, then skip the missed dose. Just take the next dose at your regular time
You should not drink grapefruit juice or eat grapefruit during treatment with ZYKADIA. It may make the amount of ZYKADIA in your blood increase to a harmful level
INDICATION
ZYKADIA™ (ceritinib) capsules is a prescription medicine that is used to treat people with non-small cell lung cancer (NSCLC) that:
Is caused by a defect in a gene called anaplastic lymphoma kinase (ALK), and
Has spread to other parts of the body, and
Who have taken the medicine crizotinib, but their NSCLC worsened or they cannot tolerate taking crizotinib
The effectiveness of ZYKADIA in these patients is based on a study that measured two types of response to treatment (response rate and duration of response). There is no clinical information available to show if patients treated with ZYKADIA live longer or if their symptoms improve. There are ongoing studies to find out how ZYKADIA works over a longer period of time.