Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC
Preliminary activity and safety results from a phase I clinical trial of PF-00299804, an irreversible pan-HER inhibitor, in patients (pts) with NSCLC
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PF-00299804（一种不可逆泛 HER 抑制剂）在 NSCLC 患者中进行的 I 期临床试验的初步活性和安全性结果
DOI：
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发表时间：
2008
期刊：
影响因子：
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通讯作者：
D. Camidge
中科院分区：
文献类型：
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作者：
P. Jänne;J. Schellens;J. Engelman;S. Eckhardt;R. Millham;L. Denis;C. Britten;Steven G. Wong;D. Boss;D. Camidge
8027背景：PF-00299804（PF）是一种口服生物利用度、强效、不可逆的HER 1、HER 2和HER 4小分子抑制剂。在NSCLC中广泛观察到HER 1过表达/异常功能，HER 1突变与肿瘤发生机制有关，并与EGFR抑制剂吉非替尼（G）和厄洛替尼（E）敏感性相关。报告了I期研究中HER基因扩增、HER 1/HER 2突变或野生型（WT）KRAS富集的难治性NSCLC患者的结果。研究方法：NSCLC患者（n=42）接受PF 16 mg（n=1）、30 mg（n=2）、45 mg、MTD（n=33）或60 mg（n=6）QD连续给药或每3周为1周期给药2周。当招募额外的HER 1突变型或KRAS WT肿瘤NSCLC患者时，NSCLC患者被纳入剂量递增阶段和MTD阶段。结果：迄今为止，已入组44例NSCLC患者（29例可评价缓解）。基线特征为：中位年龄57岁（范围26-77），既往EGFR抑制剂94%（E n=21，G n=6，E + G n=3;西妥昔单抗）。
8027 Background: PF-00299804 (PF) is an orally bioavailable, potent, irreversible small molecule inhibitor of HER1, HER2, and HER4. HER1 overexpression/aberrant function is widely observed in NSCLC and HER1 mutations are implicated in mechanisms of tumorigenesis and are associated with sensitivity to EGFR inhibitors gefitinib (G) and erlotinib (E). Results in pts with refractory NSCLC enriched for HER gene amplification, HER1/HER2 mutation, or wild type (WT) KRAS, within the phase I study are reported. Methods: NSCLC pts (n=42) received PF 16 mg (n=1), 30 mg (n=2), 45 mg, the MTD (n=33) or 60 mg (n=6) QD either continuously or for 2 weeks of a 3- week cycle. NSCLC pts were included in both the dose-escalation phase and at MTD, when additional NSCLC pts with HER1 mutant or KRAS WT tumors were recruited. Results: 44 pts with NSCLC have been enrolled to date (29 evaluable for response). Baseline characteristics were: median age 57 yrs (range 26–77), prior EGFR inhibitors 94% (E n=21, G n=6, E + G n=3; cetuxi...