阿斯利康和罗氏合作开展血浆检测egfr一线耐药后的基因检测

http://www.cambridgenetwork.co.u ... ostic-test-azd9291/

AstraZeneca and Roche announce partnership to develop companion diagnostic test for AZD9291           28/07/2014

AstraZeneca today announced it has entered into collaboration with Roche to develop a plasma-based companion diagnostic test to support AZD9291, AstraZeneca’s investigational compound in clinical development for non-small-cell lung cancer (NSCLC).
The companion diagnostic test is designed to identify epidermal growth factor receptor (EGFR) mutations in both tumour tissue and plasma derived from patients with NSCLC, and to optimise the clinical development of AZD9291 for patients who are resistant to first-generation EGFR tyrosine kinase inhibitors (TKI).

Currently, patients who have been treated with EGFR-TKIs in whom the disease has progressed have to undergo a repeat biopsy to assess whether they have a specific mutation, T790M. Diagnostic tests based on circulating DNA (ctDNA) in plasma samples provide an alternative method of identifying the T790M mutation.

Mondher Mahjoubi, Senior Vice President, Global Product Strategy for Oncology at AstraZeneca said: “We are committed to developing targeted medicines that improve health outcomes for patients. Understanding the nature of each individual’s tumour and therefore which medicine is most likely to benefit them is vital if we are to transform the way cancer patients are diagnosed and treated.”

“Currently, late-stage lung cancer patients have to undergo surgery to collect tissue from a tumor so it can be sent for molecular testing,” said Paul Brown, Head of Roche Molecular Diagnostics (RMD). “In some cases, collecting enough tissue for testing is not possible. This collaboration will enable molecular testing through plasma specimens and provide the information needed to inform treatment decisions without the complications of surgery, consequently increasing the level of care clinicians can give to the patient.”

NSCLC represents approximately 80 to 85 per cent of all lung cancers. Unfortunately, at the time of diagnosis approximately 70 per cent of NSCLC patients have developed advanced or metastatic disease not amenable to surgical resection.  

About AZD9291
AZD9291 is a highly selective, irreversible inhibitor of both the activating sensitising EGFR mutation (EGFRm+) and the activating resistance mutation, T790M, while sparing the activity of wild type EGFR. Patients with EGFRm+ NSCLC are particularly sensitive to treatment with currently available EGFR TKIs, which block the cell signalling pathways that drive the growth of tumour cells. However, tumour cells almost always develop resistance to treatment, leading to disease progression. In approximately half of patients, this resistance is caused by the secondary mutation known as T790M. There are currently no targeted therapies approved for the treatment of tumours with this resistance mutation. In the ongoing Phase I study, AZD9291 has shown early evidence of activity as a once-daily monotherapy with clinical responses observed in an EGFRm+ population of patients with NSCLC who have previously failed on EGFR TKIs and also in patients with the T790M mutation. To date, AZD9291 has been well-tolerated with low rates of side effects.

About Roche
Headquartered in Basel, Switzerland, Roche is a leader in research-focused healthcare with combined strengths in pharmaceuticals and diagnostics. Roche is the world’s largest biotech company, with truly differentiated medicines in oncology, immunology, infectious diseases, ophthalmology and neuroscience. Roche is also the world leader in in vitro diagnostics and tissue-based cancer diagnostics, and a frontrunner in diabetes management. Roche’s personalised healthcare strategy aims at providing medicines and diagnostics that enable tangible improvements in the health, quality of life and survival of patients. Founded in 1896, Roche has been making important contributions to global health for more than a century. Twenty-four medicines developed by Roche are included in the World Health Organisation Model Lists of Essential Medicines, among them life-saving antibiotics, antimalarials and chemotherapy.

In 2013 the Roche Group employed over 85,000 people worldwide, invested 8.7 billion Swiss francs in R&D and posted sales of 46.8 billion Swiss francs. Genentech, in the United States, is a wholly owned member of the Roche Group. Roche is the majority shareholder in Chugai Pharmaceutical, Japan.

For more information, please visit www.roche.com.

To read more information, click here.


AstraZeneca is a global, innovation-driven biopharmaceutical business that focuses on the discovery, development and commercialisation of prescription medicines, primarily for the treatment of cardiovascular, metabolic, respiratory, inflammation, autoimmune, oncology, infection and neuroscience diseases.

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大家可以自己用翻译软件或者自己英语看看

丁香园有个信息我转过来（原文）

AZ为其癌症药物合作开发两种新型诊断方法
2014-07-29 09:15 来源：丁香园作者：fyc5078
近日，阿斯利康分别与罗氏及Qiagen签订了开发两种不同诊断检测方法的协议，即通过利用简单的血样鉴定出哪些患者将可以受益于其肺癌药物。目前的检测方法是通过穿刺活检或术中采集组织样本对患者进行检测，然后观察患者的肿瘤中是否含有可以使他们适合药物治疗的基因突变。
新的检测方法基于智能技术，它可以检测来自患者血液血浆中循环的肿瘤DNA小碎片。与Qiagen的合作包括开发一种诊断检测方法用于伴随阿斯利康已上市的肺癌药物吉非替尼，而与罗氏的协议是开发一种伴随诊断方法用于阿斯利康试验药物——吉非替尼后续产品AZD9291。
AZD9291以一种可以帮助肿瘤逃避现有治疗药物的基因突变为靶点，阿斯利康认为这款药物的年销售额可能会达到30亿美元。这种基因突变称之为T790M，这种基因突变可使患者对目前的表皮生长因子受体抑制剂如吉非替尼变得耐药。

但愿这种检测别和基因检测一样贵

省了手术是好事，也降低了费用。只是检测精确度是关键。

关注

如果能够开发成功简单的血样鉴定基因突变检测方法，对于一线靶向用药的指导和获得性耐药的突变判断及后续方案都会更加有针对性，便于靶向药的普及和减少盲试的风险。对于广大病友是真正的福音。如果能够检测其它各种突变，而不单纯是EGFR，那就是功德无量了！

不知国内有没医院在做了?

一步错步步错 发表于 2014-7-30 11:19
不知国内有没医院在做了?

国内有一些医院在做，成熟度还不是很充分，我做过，说是用血液最好是耐药比较严重时候才行，，转移少，耐药轻（我家做的时候这两种情况都是，现在加量4个月数据还稳定，所以是阴性）容易出现假阴性。 因为血液里面的肿瘤细胞比组织少，然后血液里面突变的细胞更少，耐药突变的肿瘤细胞更少，而一种方法又有检测限，，故容易出现假阴性。

潇湘风雨 发表于 2014-7-30 11:31
国内有一些医院在做，成熟度还不是很充分，我做过，说是用血液最好是耐药比较严重时候才行，，转移少， ...

是不是只能查是否有T790,能不能查有没有CMET?

几个背景信息

首先，AZ在ASCO 2014上面有一个关于EGFR耐药ctDNA检测的临床结果发表:
http://meetinglibrary.asco.org/content/127956-144

EGFR mutation detection in ctDNA from NSCLC patient plasma: A cross-platform comparison of technologies to support the clinical development of AZD9291.

里面采用了4种方法来检测ctDNA

Methods: Using plasma from patients enrolled on the AZD9291 clinical study (NCT01802632), we undertook a cross-platform comparison of 4 methods for the detection of EGFR mutations in ctDNA:
1. ARMS-based detection using Roche Cobas
罗氏Cobas的基于ARMS的检测，ARMS就是吴一龙提到的扩增阻碍突变系统(Amplification refractory mutation system)
2. Qiagen Therascreen EGFR mutation detection kits
Qiagend Therascreen EGFR突变检测试剂盒
3. digital PCR-based (dPCR) approaches using BioRad ddPCR (MolecularMD)
BioRad的数字PCR
4. BEAMing (Inostics)
BEAMing技术(数字PCR-流式技术)

结果有点意思：
In contrast, dPCR methods showed increased sensitivities for T790M compared with the ARMS-based methods (67-71% vs. 29-41%) whereas sensitivity for activating mutations was equivalent between dPCR and ARMS (80-90%).
dPCR技术对T790M检测的敏感度高于ARMS方法(67-71% vs. 29-41%)

待续