是不是现在大家都用9291代替4002啊？

4002有效，还是继续用，不舍得换成9291.

我家也是，继续4002

奔四的顽石 发表于 2014-5-22 21:36
4002有效，还是继续用，不舍得换成9291.

4002耐药后，9291还能作为后续用药吗？

4002耐药后，9291还能作为后续用药吗？
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我觉得这点还是挺有意思的: 4002不产生T790M。4002耐药后，还值得用9291吗？ 我不懂，就是问问。

darkeyeswf 发表于 2014-5-25 11:02
4002耐药后，9291还能作为后续用药吗？

我也不清楚是否有用，只是现在吃得好好的，不想马上换。

又想了想，

1）如果单独服用WZ4002从有效到无效，此时可以用AZD9291，寄希望打击E靶点。

2）如果易/特联用WZ4002从有效到无效，因为WZ4002的失效，易/特的使用或许产生新的T790突变。此时可以用AZD9291，寄希望打击E靶点和T790M。

。。。。。。
AZD9291 is an oral, irreversible, third generation, selective inhibitor of both EGFR activating (EGFRm+) and resistance (EGFRm+/T790M) mutations.
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   ---参考http://mct.aacrjournals.org/cont ... nt/A109.short?rss=1

AZD9291是一种口服的，不可逆的，第三代，选择性抑制剂，抑制EGFR激活性突变和EGFR/T790M耐药性突变。




原文：
Abstract A109: AZD9291: an irreversible, potent and selective third generation tyrosine kinase inhibitor (TKI) targeting EGFR activating (EGFRm+) and resistance (T790M) mutations in advanced lung adenocarcinoma.

Abstract

The first generation EGFR TKIs gefitinib and erlotinib provide significant clinical benefit in patients with advanced lung adenocarcinoma harbouring activating EGFR mutants (EGFRm+), but patients will ultimately develop disease progression due to acquired resistance. Acquisition of the EGFR T790M mutation is the most common mechanism of drug resistance, detected in more than 50% of gefitinib/erlotinib resistant patients. Current therapeutic strategies are limited for advanced lung adenocarcinoma patients with EGFR T790M (EGFRm+/T790M), so this remains a key area of unmet need. AZD9291 (structure to be disclosed at meeting) is an oral, irreversible, third generation, selective inhibitor of both EGFR activating (EGFRm+) and resistance (EGFRm+/T790M) mutations. The mechanistic and functional activity of AZD9291 was characterised in vitro and in vivo across a number of cell lines harbouring various EGFR-mutations or wild type EGFR. Presented data shows AZD9291 potently inhibits EGFR phosphorylation in EGFRm+ (e.g. PC9; <25nM) and EGFRm+/T790M (e.g. H1975; <25nM) cell lines in vitro, whilst demonstrating much less activity against wild-type EGFR lines (e.g. LoVo; >500nM). Consistently, AZD9291 showed significantly more potent inhibition of proliferation in mutant EGFR cell lines compared to wild-type in vitro. In addition, AZD9291 administered once daily orally at 5mg/kg caused profound regression of tumours across EGFRm+ (PC9; 178% growth inhibition) and EGFRm+/T790M (H1975; 119% growth inhibition) tumour models in vivo, after 14 days dosing. Furthermore 5mg/kg AZD9291 was sufficient to cause significant shrinkage of EGFRm+ and EGFRm+/T790M transgenic mouse lung tumours. Tumour growth inhibition was associated with profound inhibition of EGFR phosphorylation and key downstream signaling pathways such as AKT and ERK. Chronic long-term treatment of PC9 and H1975 xenograft tumours with AZD9291 led to a complete and sustained macroscopic response, with no visible tumours after 40 days dosing, and being maintained beyond 100 days. Furthermore, pre-clinical data also indicates that AZD9291 could target tumours that have acquired resistance to the more recently identified HER2-amplification mechanism, thus potentially extending its benefit in TKI resistant patients. Taken together, preclinical data demonstrates that AZD9291 is a potent and effective inhibitor of both EGFR activating (EGFRm+) and resistance (EGFRm+/T790M) mutations whilst sparing wild-type EGFR. These data support the further clinical investigation of AZD9291 in advanced EGFR mutant lung adenocarcinoma.

Citation Information: Mol Cancer Ther 2013;12(11 Suppl):A109.

我家4002联特吃了七个月，4002接近耐药，现在吃9291联特中，还没有检查，不过应该是有效的。