辉瑞的PF00299804的二个三期临床失败

Pfizer lung-cancer drug fails in two Phase III studies
Pfizer's (PFE -0.3%) Dacomitinib drug has failed in two Phase III trials of patients with refractory advanced non-small cell lung cancer.In the ARCHER 1009 trial, which included patients previously treated with chemotherapy, Dacomitinib did not significantly improve progression-free survival (PFS) when compared with the Erlotinib (Tarceva) drug.In the second study, Dacomitinib was unable to lengthen survival vs a placebo.A third Phase III trial is assessing Dacomitinib in a different patient population, with the results expected in 2015.

啊 怎么会这样呢。。。。但是国外人种和国人不同 具体实验的内容方式也没说 希望还是有很多情况下可以用到

我们家吃dacomitinib也无效的，估计此药对her2突变效果不行。有效否，估计还得看her2的IC50吧（Afatinib, Poziotinib)，经验之谈。

要在EGFR靶点上胜过特罗凯本来就很难。当初2992是拿特罗凯做对比的吗？凯美纳的临床试验也只挑了易瑞沙做对比。

坛子里不是有很多用原料299804来控制脑转的吗？反应还不错呀！我本打算把这武器放在后面治疗阶段呢。

Pfizer Announces Top-Line Results From Two Phase 3 Trials Of Dacomitinib In Patients With Refractory Advanced Non-Small Cell Lung Cancer

An Ongoing, Third Phase 3 Trial is Evaluating Dacomitinib in First-Line in EGFR-Mutant NSCLC  

Monday, January 27, 2014 - 7:00am EST
Pfizer Inc. today announced top-line results from two randomized Phase 3 studies of the irreversible pan-HER kinase inhibitor dacomitinib in patients with advanced non-small cell lung cancer (NSCLC).

Both trials evaluated dacomitinib in populations of previously treated patients with advanced NSCLC.  The ARCHER 1009 trial, which included patients previously treated with chemotherapy (second/third line), did not meet its objective of demonstrating statistically significant improvement in progression-free survival (PFS) when compared with the EGFR inhibitor erlotinib.

Separately, the NCIC CTG BR.26 trial, which included patients with advanced NSCLC after standard therapy with both chemotherapy and an EGFR tyrosine kinase inhibitor had failed, did not meet its objective of prolonging overall survival (OS) versus placebo.

An ongoing, third Phase 3 trial, ARCHER 1050, is evaluating PFS of dacomitinib in a different patient population than was studied in ARCHER 1009 and BR26.  ARCHER 1050 compares dacomitinib versus gefitinib in treatment-naive (without prior treatment) patients with EGFR-mutant advanced NSCLC.  The results are expected in 2015.                                   

“While we are disappointed in the results, lung cancer is a complex disease, and the use of targeted agents to treat specific patient populations continues to evolve,” said Dr. Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology.  “We are analyzing the findings from both ARCHER 1009 and BR.26 to better understand the effects of dacomitinib in molecularly defined subgroups of patients with advanced NSCLC, including those with EGFR mutations.”  

The ARCHER 1009 trial evaluated dacomitinib versus erlotinib in two co-primary populations of patients with advanced NSCLC previously treated with at least one chemotherapy regimen – all patients and patients with KRAS wild-type NSCLC.  The study did not demonstrate that dacomitinib improved PFS in either of the co-primary populations compared to erlotinib.  

The BR.26 trial was a double-blind, placebo-controlled, randomized study evaluating dacomitinib in patients with locally advanced or metastatic NSCLC after prior treatment, which included at least one chemotherapy regimen and one EGFR inhibitor treatment regimen.  This study was designed, conducted and led by NCIC Clinical Trials Group (NCIC CTG).

“We are pleased to have had the opportunity to assess dacomitinib in the BR.26 trial,” said Dr. Peter Ellis, BR.26 Study Chair and Associate Professor in the Department of Oncology, McMaster University, and medical oncologist at the Juravinski Cancer Centre, Hamilton, Ontario, Canada.  “While we are disappointed that the trial did not meet its primary endpoint, we are supportive of Pfizer’s commitment to continue to evaluate dacomitinib in the ARCHER 1050 trial.”

In both studies, the adverse events observed for dacomitinib generally were consistent with its known adverse event profile.  Full efficacy and safety data from ARCHER 1009 and BR.26 will be submitted for presentation at an upcoming medical meeting.

信源：http://www.pfizer.com/news/press ... ll_cell_lung_cancer

其实大致能够看出一些问题

ARCHER 1009是一线化疗以后和特罗凯作头对头的研究，注意这里提到的“which included patients previously treated with chemotherapy (second/third line)”，表明这是将804用于二线甚至三线的治疗，而2992的批准依据是一线和化疗的对比临床(参见这里)，目前还没有有力的证据表明不可逆TKI(804/2992)在一线(化疗)以后的表现优于可逆TKI(易/特)，更何况还有存在未选择适应人群的情况

而BR.26入组的患者是之前接受过一个化疗疗程和一个EGFR TKI(易/特)的疗程，这相当于是在患者对化疗和一种EGFR TKI都耐药之后，再用804和安慰剂做对比，辉瑞也清楚，要压过2992，只有在多线应用之后做文章，和2992头对头目测是占不到什么便宜的，可惜从咱们论坛病友的使用情况来看，在已对一种EGFR TKI耐药之后，再用2992/804效果都不尽人意，所以我个人觉得这个临床失败也是在情理之中

正在进行中的ARCHER 1050是一线和易作头对头的对比，我觉得辉瑞开这个临床也是想留一个保底的，可能它自己也考虑到前面两个失败的情况，期待2015年的结果吧，作为入脑概率较高的一款TKI，还是不希望就这样倒在3期了

一线PFS比不过特罗凯很正常。对于EGFR突变患者，易、特一线用药的位置目前不可动摇。

看到这个消息真是突然，本来寄予很大希望。299804用到第二个月CEA升高，第三个月没有马上停待测。是不是意味着804已可基本确定无效，用2992也意义不大。