阿斯利康的T790M牛逼新药AZD9291的1期临床结果出来了

这个用量少，YL药价格将来不知道会便宜些

药的有效率有多高?药能吃多久?这是关键?

那个PDF，我大致看了一下，是以CLVS角度发表的，所以通篇我觉得怎么都在说CO1686的好？另外，我比较想看阿斯利康角度发表的文章或者第三方的，比较客观。那篇PDF不出意外我会周六翻译上来

看不懂 看不懂 哎

谢谢老马和UICKI

Clovis Oncology: CO-1686 (Phase I/II/NSCLC) is Wild-Type EGFR Sparing and Appears to Be More Selective vs.
AstraZeneca’s AZD9291
CO1686对EGFR野生型无效，较AZD9291相比更具选择性。

As we head into ESMO this weekend, we conducted an analysis of the pre-clinical data on AZD9291, the closest competitor to Clovis’ CO-1686 in lung cancer patients with the T790M resistance mutation.
本周我们从欧洲肿瘤学会上获悉，我们引导了AZD9291临床前期的数据，其是同样阻止肺癌病人T790m突变的CO1686的最强有力的竞争对手。
A key question for investors is how active is AZD9291 against T790M vs. wild-type EGFR.
对于投资者而言，关键问题是对于EGFR野生型来说，AZD9291对于阻止T790M突变有多大的活性。
Based on our preliminary analysis of available pre-clinical data, AZD9291 does not spare wild-type EGFR as selectively compared to CO-1686.
根据我们有效的初步前期实验室数据小结，相较于CO1686，AZD9291可选用于EGFR野生型的治疗。
While there is less data to make a comparison on the relative potency at T790M, the drug does have activity based on preclinical data, but activity could be impacted by dose limiting side effects.
与此同时，（两者）对于T790M相关有效力的比较数据却甚少，多少剂量用药会产生活性完全取决于前期实验室的数据，但剂量限制性副作用将会对药物活性产生影响。
We expect to get a better sense of the competitive landscape this weekend at ESMO, when we will get our first glimpse at the AZD9291 phase 1 clincal data.  
我们期许能在欧洲肿瘤学会上对两者的比较有一个更好的感观了解，介时我们将瞥一眼AZD9291在实验室的I期试验。
AZD9291 Wild-Type EGFR Activity May Be Dose Limiting. Based on our preliminary analysis of the AZD9291 pre-clinical data, we believe that the compound has the potential to show dose limiting toxicity associated with wild-type EGFR inhibition.
AZD9291用于EGFR野生型的治疗可能会受剂量限制。基于我们对AZD9291前期实验室数据的小结，我们相信这样一种合成物对于野生型的EGFR的抑制具有潜在的剂量限制毒性。
In pre-clinical mouse lung xenograft models, AZD9291 had 78% tumor growth inhibition in wild-type cells which is similar to Iressa (gefitinib) which had 62% tumor growth inhibition in wild-type cells (see figure 1 on page
2).
在前期实验室的小鼠肺异种移植模型上，AZD9291在野生细胞中对78%的肿瘤生长有抑制作用，这一数据同易瑞沙在野生细胞对62%的肿瘤生长抑制是相接近的。
Given that Iressa is associated with known GI toxicity and skin rash, due to wild-type EGFR inhibition, similar side effects could be dose limiting and potentially limit the therapeutic window of AZD9291, while CO-1668 is already showing decent potency (3/4 PR in T790M mutations) without toxicity issues so far and is still in the dose escalation phase which bodes well from an efficacy perspective.  
我们都知晓易瑞沙具有I级毒性和造成皮疹，因为是野生型EGFR抑制剂，相同的副作用可能是剂量限制性的也将潜在限制AZD9291的治疗窗（不少药物的代谢和反应具有种族差异,药物代谢和反应 种族差异的临床意义取决于药物治疗窗），而CO1668已经在目前为止没有毒性事件的情况下展现出其出色的表现，其增量试验也在进行中且功效前景预估良好。
CO-1686 is Wild-Type EGFR Sparing and More Selective. We believe CO-1686 could potentially be more selective than AZD9291 as the drug targets activating EGFR mutations and the T790M resistance mutation, but spares wild-type EGFR at anticipated therapeutic doses.
CO-1686对EGFR突变有效（原句为对野生无效）且更具选择性。我们相信，作为作用于EGFR突变和阻止T790M突变的药而言，CO1686比AZD9291更具潜在的选择性，但野生型EGFR则被排除在参与治疗的剂量之外。
In a recently published analysis, CO-1686 had almost no activity against wild-type
EGFR compared to existing earlier generation tyrosine kinase inhibitors such as Tarceva (erlotinib) and Gilotrif(afatinib).
在最近一期发表的小结上，CO1686相比已有的较早一代的酪氨酸激酶如特罗凯和阿法替尼相比，对于对抗野生型的EGFR基本无任何活性。
This difference in selectivity may drive CO-1686 to have a better toxicity profile compared to AZD9291, which could lead to a better therapeutic window.  
这一选择上的区别可能使CO1686在毒性危害上，与AZD9291相比更小一些，而这将使CO1686有更好的治疗窗。
CO-1686 Market Opportunity Attractive. We model only 50% penetration into the T790M mutation population as 2nd-line therapy and factor in competition. We assume a 65% probability of success in this indication given the current data,
and the drug's mechanism of action. We model approval in 2017 and global probability adjusted peak sales of $517M in 2033.  
（这一段是对未来的展望，经济上的，不翻了）

谢谢υīСКī，那也就是说，对于EGFR  有突变的人来说，CO1686比AZD9291有更好的治疗窗。

用心良苦 发表于 2013-10-12 23:32

                               
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谢谢υīСКī，那也就是说，对于EGFR  有突变的人来说，CO1686比AZD9291有更好的治疗窗。

对，另外还有剂量方面，1686比9291ms毒性小，当然这个只是clvs一家之言，目前来看两者各有长处，难分伯仲

非常感谢！

关于9291的： Got some additional info today. Early phase I was pretty encouraging. Most of the responders was only with 20mg per day dose. Dose escalation was up to 160mg per day without severe adverse effects in most.