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
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