本帖最后由 costa_na 于 2014-1-28 00:14 编辑
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
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