讨论：美国接受PD-1治疗- Opdivo, Keytruda

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本帖最后由 pigbubu 于 2015-5-13 02:03 编辑

正在查资料，怎么去美国接受PD-1免疫疗法治疗非小细胞肺癌

近期会更新这个帖子，把找到的资料翻译了和大家分享。对于单克隆抗体来说，
很难通过非医生处方拿到药，所以就不讨论这种可能了。

现在也有出国医药公司提供赴美就医全套的服务，包括翻译病历，联系医院，联系食宿等等，有钱的人家可以考虑找他们省事。
这里就只讨论自己联系预约美国医院医生进行治疗的，因为光是百万药费的负担已经够重的了。

有信息错误欢迎指正，希望大家和亲属都健康

1. Opdivo：
BMS生产的，FDA今年三月已经批准于非小细胞肺癌，
所以现在去美国医生可以合法治疗。

原理：人体单克隆抗体，阻止PD-1和PD-L1/PDL2的结合，抗体结合PD-1引起癌细胞凋亡
用于：含铂化疗进展后的鳞状细胞非小细胞肺癌

针剂规格： 40mg/4mL ($1077) 和100mg/100 mL ($2691)

用法，用量，价格：
每两周注射一次，每次用量3mg/kg体重，每次注射时间60分钟。

50kg- 每次150mg，一个月两次，每个月药费~$9700 美金，6万人民币。一年13万美金，78 万人民币
60kg- 每次180mg
70kg- 每次210mg
80kg- 每次240mg, 一个月两次，每个月药费~$13,000 美金，8万人民币。一年17万美金，105万人民币。

副作用：
咳嗽，胸痛，气短，肺炎
腹泻，便血，腹痛
肝炎

2. Keytruda
Merck生产的，批准用于黑色素瘤，肺癌的还没批，不能合法的用
像有的帖子说的去香港找一个医生off-label开，就是说虽然病人有肺癌，病例写成黑色素瘤来开药，这里不讨论。

剂量：现在批准的黑色素瘤用量是 2mg/kg, 每三周一次
正在进行临床试验的NSCLC，普遍使用剂量是200mg每次，每三周一次
针剂零售价格是 ~$4300/100 mg,
如果按照200mg/三周，每年的价格是15万美金。

到美国治疗的其他费用：
1. 医院、医生、诊所的诊疗费，检查费用

每次诊费可能要$500以上。
CT 检查每两个月一次，可能要接近$1000美金，
每两周用药可能都要化验学和心电图，估计要$1000
等我具体研究了再上来报告。
医院对个人收费价格都是比对保险价格高很多的。据说没有保险能要求医院打折。

2. 食宿，往返机票
据出国医疗中介网站写，住宿不同城市$3000-5000一个月，饮食两人每月$1000左右
往返机票两人$2000-$3000

pigbubu · 发表于 2015-5-12 01:33:53

http://www.rxeconsult.com/health ... nced-Melanoma--760/

Opdivo (nivolumab) Side effects, Cost, Approval and Prescribing Information for Advanced Melanoma - See more at: http://www.rxeconsult.com/health ... thash.C7vj6ZDI.dpuf

Brand Name: Opdivo
Generic Name: nivolumab

Medication Class: Humanized monoclonal antibody blocking the programmed human death receptor 1 (PD-1)
Similar Drugs: Keytruda (pembrolizumab)
Manufacturer: Bristol-Myers Squibb
Approval Date: December 2014

What is Opdivo and its mechanism of action?

Opdivo is a humanized monoclonal antibody that blocks the interaction between programmed death receptor 1 (PD-1) and its ligands (PD-L1 and PD-L2). If you suppose a receptor is a lock, the ligands are the corresponding keys to the lock. Likewise, the PD-1 is a lock and the ligands are the keys that fit right into PD-1. When the ligands interact with PD-1 it sends a signal to cells to go through programmed cell death. In other words, the cell commits suicide.

PD-1s present on immune cells called T cells. Normally T cells produce chemicals to attack any harmful substances in the body. However, when ligands interact with PD-1s on T cells the T cells shuts down and die. Many cancer cells express the ligands (PD-L1) and send it to T cells to prevent an immune response to the cancer. Opdivo selectively binds to PD-1 and blocks the interaction between PD-1 and its ligands. Therefore it allows the T cells to survive and fight off the cancer.

What is Opdivo used for treating?

Opdivo is indicated for patients with metastatic squamous non-small cell lung cancer with progression on or after platinum-based chemotherapy.

It is also used for treating advanced stage melanoma (skin cancer) which:
•Cannot be removed with surgery (unresectable)
•Has spread to other parts of the body (metastasized)
•Have failed treatment with ipilmumab (another cancer treatment for melanoma)
•Showed positive for BRAF mutations (involved in abnormal cell growth)
•Have failed treatment with BRAF inhibitors

How effective is Opdivo treating melanoma?

The clinical trial was conducted in patients with metastatic melanoma who had progression of disease after treatment with ipilimumab, a BRAF inhibitor, or if BRAF gene mutation positive. Patients received Opdivo by intravenous infusion at 3mg/kg every 2 weeks or some other chemotherapy such as dacarbazine 1000mg/m2 every 3 weeks or the combination of carboplatin every 3 weeks plus paclitaxel 175mg/m2 every 3 weeks.

The efficacy of Opdivo was evaluated for the first 120 patients who had a minimum of 6 months follow up. Among the 120 patients treated with Opdivo, 32% responded; 4 were complete responders and 34 partial responders. Amongst 38 responders, 33 patients had on going response with duration ranging from 2.6+ to 10+ months. The FDA granted an accelerated approval to Opdivo for metastatic melanoma treatment based on tumor response rate and durability of response.

Interesting fact about Opdivo
•Opdivo is the second programmed death receptor-1 (PD-1) inhibitor approved by the FDA. Keytruda (pembrolizumab) was approved in September 2014. The interaction between PD-1 and its ligands suppresses the body’s immune system. By blocking the interaction between PD-1 and the ligands, Opdivo allows the immune system to attack and fight off the tumor.
•The FDA granted Opdivo an accelerated approval based on the clinical trial data to allow patients with serious or life-threatening conditions to receive earlier access to this promising drug. Additional clinical studies are being conducted by the company to prove safety and efficacy of Opdivo.
•Another clinical trial of Opdivo was successfully completed on January 13, 2015. The study included 234 patients with advance lung cancer called squamous cell non-small cell lung cancer and Opdivo was compared with docetaxel, another cancer treatment. It showed that patients who received Opdivo had superior overall survival rates. The study was concluded two years earlier than planned.

What are side effects of Opdivo?

The common adverse reactions reported in the clinical trials include skin rash (21%), cough (17%), upper respiratory tract infection (11%), hyperkalemia (increase in potassium level; 15%), hyponatremia (decrease in sodium level; 25%), ALT elevation (liver enzyme; 16%), and serum creatinine elevation (kidney function; 13%).

More serious adverse reactions include hyperthyroidism, hypothyroidism (change in thyroid level; 2-8%), immune-mediated hepatitis (liver problems; 1.1%), immune-mediated gastrointestinal problems (such as pancreatitis or colitis; 1%), neuropathy (less than 1%), immune-mediated nephritis (renal dysfunction; 0.7%), and immune-mediated pneumonitis (lung problems; 2.2%).

What is the dosage of Opdivo?

Opdivo is supplied in either a 40 mg/4 mL single-use vial or a 100 mg/10 mL single-use vial. The recommended dose of Opdivo is 3 mg/kg by intravenous infusion over 60 minutes every 2 weeks until disease progression or unacceptable toxicity.

Opdivo should be stored under refrigeration at 2’C to 8’C and protected from light by storing in the original package until use.

What are Opdivo drug interactions?

There is no formal pharmacokinetic drug-drug interaction study for Opdivo.

What are warnings and precautions for Opdivo?

Since Opdivo is a medication that works on the immune system it can also cause the immune system to attack normal organs and tissues. Patients should contact the healthcare provider right way if symptoms of the following problems develop or get worse:
•Lung problems (pneumonitis): new or worsening cough, chest pain, and shortness of breath.
•Intestinal problems (colitis): diarrhea, blood in stools, severe stomach pain or tenderness.
•Liver problems (hepatitis): yellowing of skin, severe nausea or vomiting, pain on the right side of the stomach area, drowsiness, dark urine, bruise more easily, and feeling less hungry than usual.
•Kidney problems (nephritis): decrease in the amount of urine, blood in urine, swelling in ankles, loss of appetite.
•Hormone gland problems: unusual headache, extreme tiredness, weight gain or weight loss, changes in mood or behavior, dizziness or fainting, hair loss, feeling cold, and constipation.

Can pregnant women take Opdivo?

There are no adequate studies of Opdivo in pregnant women. Animal studies have shown spontaneous abortion and premature infant death when administered to monkeys twice weekly. Based on the mechanism of action and the animal studies, Opdivo can cause fatal harm when administered to a pregnant woman. It is recommended to use effective contraception for at least 5 months after the last dose of Opdivo treatment.

What is the cost of Opdivo?

The estimated retail price for 40 mg/4 mL vial is $1077 per vial, and 100 mg/10 mL vial is $2691 per vial. The manufacturer of Opdivo, Bristol-Myers Squibb, provides Patient Access Support to help patients medication cost.
- See more at: http://www.rxeconsult.com/health ... thash.C7vj6ZDI.dpuf

pigbubu · 发表于 2015-5-12 02:03:44

转自丁香园2015年三月新闻
yao.dxy.cn/article/102772

3月4日，美国FDA批准Opdivo(nivolumab)新适应症，用于治疗晚期（转移性）鳞状非小细胞肺癌(NSCLC)患者，适用于以铂类为基础化疗或化疗后疾病出现恶化的患者。

肺癌是美国癌症死亡的主要因素，2014年有22.421万人被确诊患有这种疾病，有15.926万人因该病死亡。非小细胞肺癌是最常见形式的肺癌，它影响八分之七的肺癌患者，当癌症在肺细胞形成时就会发生这种疾病。

Opdivo通过抑制细胞上一种叫PD-1蛋白的细胞通路而发挥作用，PD-1蛋白可阻断人体免疫系统对癌细胞进行攻击。Opdivo适用于先前已使用铂类为基础化疗治疗的患者。

“当试验数据在去年12月底可供使用时，FDA为促使这一重要临床试验数据的提交与审评，该机构积极与公司开展合作，”FDA药品评价与研究中心血液及肿瘤产品办公室主任、医学博士Pazdur称。“此次批准将为患者及卫生保健供应商提供与Opdivo相关的生存期优势知识，将帮助指导患者护理及未来的肺癌临床试验。”

Opdivo治疗鳞状非小细胞肺癌的疗效基于随机试验的272名受试者，他们当中有135人接受Opdivo治疗，有137人接受多西他赛治疗。这项试验旨在测试患者在开始治疗后其生存时间。平均来说，接受Opdivo的患者存活了32个月，长于那些接受多西他赛治疗的患者。

Opdivo治疗鳞状非小细胞肺癌的安全性及有效性通过一项单组试验得到支持，试验的受试者为先前接受铂类为基础治疗及至少一种其它系统方案治疗后疾病出现恶化的患者。这项研究旨在检测客观缓解率(ORR)，即经历肿瘤部分缩小或完全消失受试者的百分数。结果显示，15%的受试者经历了ORR，其中59%的患者有6个月或更长时间的响应。

Opdivo最常见的副作用是疲劳、呼吸急促、肌肉骨骼疼痛、食欲下降、咳嗽、恶心和便秘。最严重的副作用是严重免疫介导副作用，涉及到健康器官，包括肺、结肠、肝脏、肾脏及产生激素的腺体。

Opdivo用于鳞状非小细胞肺癌是在FDA优先审评程序下完成评价的，这一审评程序为治疗严重疾病的药物提供了一个加快的审评，如果该药物获得批准，它将在安全性及有效性上对一种严重疾病的治疗提供明显改善。Opdivo的获批时间与其申请者付费法案目标日期2015年6月22日相比提前了3个多月，后者是FDA计划完成该药物上市申请审评的日期。

FDA之前已批准Opdivo治疗不再对其它药物响应的不可切除或转移性黑色素瘤患者。Opdivo由美国新泽西州普林斯顿的百时美施贵宝上市销售。