C797S and MET are the two most common resistance mutations after osimertinib？
Necitumumab
http://www.abstractsonline.com/pp8/#!/4292/presentation/5469
另一个三代耐药的情况
EGFR wildtype
http://www.abstractsonline.com/pp8/#!/4292/presentation/6912
I had my 4 year cancerversary in late May and since that date all medical news is negative. Just to summarize rapidly I am treated for an adenocarcinoma of the lung (I also have an SCLC but it seems quiet for the time being) and was EFGR mutated for the last four years. I was on Erlotinib, Osimertinib and then Afatinib. I tried bevacizumab, cetuximab and panitumumab unsuccessfuly when my cancer progressed. In March, I started a chemo (carboplatin+alimta for four cycles and Alimta as maintenance afterwards), which shrunk my lesions after two cycles but the control Petscan made last Tuesday showed a new very active lesion in the lung, several new nodules in the lung and four of my 15 bone metastases with increased hypermetabolic activity.
https://www.ncbi.nlm.nih.gov/pubmed/28278517
关于标志物
intedanib targets vascular endothelial growth factor receptor (VEGFR), fibroblast growth factor receptor (FGFR) and also platelet derived growth factor receptor (PDGFR), so the spectrum of inhibition is wider.
do brain MRI regularly because if you catch a brain lesion early, you can zap it easily with GammaKnife
idiopathic pulmonary fibrosis特发性肺纤维化，用nintedanib ，也被推荐与多西他赛联用。
Nintedanib是monoclonal antibody
EGFR19 T790M EGFR19的情况，开始用Gefitinib had good response，后发现brain & leptomeningeal metastasis（脑脊柱），用RT治疗两个 intra-axial brain metastasis 但不是全脑放疗，PET扫描发现multiple bone metastasis。停止Osimertinib 开始脉冲tarceva 600mg twice weekly，加上Bevasizumab (Avastin) 900mg (15mg/kg).。had good response。
MET amplification. This seems to be a common resistance mechanism in the brain for many patients with EGFR.
PTEN mutations found on the Guardant report give us a clue: maybe these are the reason for resistance and the AKT-mTOR pathway is activated as a result.
上述例子，如果是PTEN的情况，那么可以考虑EGFR和MTOR抑制剂联用，一开始先上正常剂量，之后可以考虑增加剂量并做间歇疗法（intermittent treatment ）？
对于上述例子给出的一些方法 ：
https://www.inspire.com/groups/a ... e=37&ga=freshen
Carboplatin, Pemetrexed and Pembrolizumab可以作为NSCLC的一线（）
EGFR T790M 之后在所有基因都不突变（所有TKI都无效的情况下），有过考虑了上述的疗法，FDA已批准。
注：卡铂+培美之前用过有effect
http://www.ascopost.com/News/55616
有加倍Tagrisso 之后没有new brian met出现的情况（之后还对已有的进展的brian met进行了Gamma Knife treatment t），有brian met不意味着progression。
软脑膜转yi leptomeningeal metastases that the standard treatment for lepto is radiation, or -in the case of EGFR patients- pulsed erlotinib or double dose osimertinib.
some oncologists recommend intrathecal chemo and whole brain radiation. Some other oncologists recommend WBR plus either gemcitabine or paclitaxel, which can cross the blood-brain barrier, once it is disrupted by radiation. Apparently the co-administration of radiation and gemcitabine (or paclitaxel) allows the chemo drug to reach tumours within the CNS.
RET和MET靶向与依维莫司联用，跨越BBB效果well。
ATM 遗失（删除）有案例用Mekinist/Tafinlar联用的
如果耐药突变是L718Q突变、C797S突变或L844V突变，使用喹唑啉母环结构的易瑞沙、特罗凯或阿法替尼可能有效
贝伐联合培美可以提高有效率，单贝伐的有效率要低很多
tagrisso有Tarceva+Cabozantinib的
原则上用药先单药再联合，9291之后可以先上易瑞沙，无效再尝试联用。（具体使用是9291+易 还是直接易不好说）
考虑到tagrisso回gefitinib可能性小，92连阿法或者阿法可以尝试先。
考虑到不止一个靶点突变，联用有时也是合理的。
2992对T790的抑制强度比较弱，需要比较大的剂量才成。
随着T790M突变细胞的增加，2992就无效了。
299804和2992是一样的机制。
Pd-1+化疗是FDA推荐预防bao fa 进zh。
Pd-1+化疗一处骨转，其他处骨转也会减少。
em:
chemo targrisso 效果不错 inspire 50
dabrafenib
BRAF is a driver similar to eg EGFR.
reatment for braf mutant lung cancer has just been approved:
FDA also approved the Oncomine™ Dx Target Test to determine the presence of the BRAF V600E mutation in patient samples
https://www.cancer.gov/news-even ... 2017/fda-trametinib -dabrafenib-lung-cancer
XL184 对野生突变类型的作用？
adding Avastin to Tagrisso
（XL）Cabozantinib in Patients With RET Fusion-Positive Advanced Non-Small Cell Lung Cancer and Those With Other Genotypes: ROS1 or NTRK Fusions or Increased MET or AXL Activity
Cabozantinib联合opdivo？
单afatinib 有过效果很好的
http://www.medsci.cn/article/show_article.do?id=cdad100e2891
关于asco MDM2 ALRN-6924 tp53(突变)
9291对耐药突变T790M有特效，而对原突变EGFR还不如特罗凯
一般有骨转的人会有耐药CMET,9291联184或联280会有效；804是控制脑转的，靶点有EGFR、T790M、HER2
804入脑效果强肺部弱，而2992肺部强而入脑弱
EGFR TKI联合BKM120可以克服HGF过表达导致的EGFR耐药问题，对于T790M或者cMet扩增导致的EGFR耐药病人，PI3K/Akt信号通路上调，EGFR TKI联合BKM120有一定效果。
PI3K 在6%-12% xian ai zhong
关于Stereotactic Radiosurgery和whole brain radiation 的选择：
P70
耐药突变也许多点突变
2992对20突变可能有一定疗效？
有t突变但是92无效，有联cabozantinib的？？？
Cabo v靶点
有t用afatinib ？？
Cdk medicine new
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显身卡
