A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib.
A phase 2 trial of dacomitinib (PF-00299804), an oral, irreversible pan-HER (human epidermal growth factor receptor) inhibitor, in patients with advanced non-small cell lung cancer after failure of prior chemotherapy and erlotinib.
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DOI：
10.1002/cncr.28561
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发表时间：
2014-04-15
期刊：
影响因子：
6.2
通讯作者：
Jaenne, Pasi A.
中科院分区：
文献类型：
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作者：
Reckamp, Karen L.;Giaccone, Giuseppe;Camidge, D. Ross;Gadgeel, Shirish M.;Khuri, Fadlo R.;Engelman, Jeff A.;Koczywas, Marianna;Rajan, Arun;Campbell, Alicyn K.;Gernhardt, Diana;Ruiz-Garcia, Ana;Letrent, Stephen;Liang, Jane;Taylor, Ian;O'Connell, Joseph P.;Jaenne, Pasi A.
这项2期试验(ClinicalTrials.gov ID NCT00548093)评估了达科米替尼(PF-00299804)对KRAS野生型非小细胞肺癌患者的疗效、安全性和对健康相关生活质量的影响。达科米尼是一种人表皮生长因子受体1、2和4的不可逆酪氨酸激酶抑制剂。晚期非小细胞肺癌、接受1到2个化疗方案和厄洛替尼的进展、KRAS野生型或已知的EGFR敏感型突变肿瘤以及东部合作肿瘤组表现状态为0至2的患者接受达科米替尼45毫克每日一次，连续21天为一个周期。共纳入66例患者(腺癌，n = 50例；非腺癌患者，n = 16例)。腺癌患者(主要终点)的客观有效率为5%(2例部分缓解；单侧P = 为372无假说[H0]：ORR≤5%)，非腺癌患者为6%(1例部分缓解)。应答者包括：25个EGFR突变阳性肿瘤中的2个；3个带有HER2扩增的EGFR野生型中的1个。EGFR突变阳性肿瘤患者的中位无进展生存期为12周(n = 66)和18周(n = 26)。与治疗相关的常见不良事件为1级或2级，可通过标准的支持护理加以控制，包括腹泻(3级[G3]，12%)、痤疮样皮炎(G3，6%)、剥脱性皮疹(G3，3%)、皮肤干燥(G3，0%)、疲劳(G3，3%)和口腔炎(G3，2%)。6名患者(9%)因治疗相关的不良事件而停用。根据患者报告，NSCLC的呼吸困难、咳嗽和疼痛(胸部、手臂/肩膀)症状在治疗3周后首次出现改善。达科米替尼在大量预治疗的患者中显示出初步的活性和可接受的耐受性，并可能在分子定义的患者亚群中提供益处。癌症2014；120：1145-1154。©2014作者。《癌症》由威利期刊公司代表美国癌症学会出版。这项研究调查了达科米替尼治疗晚期难治性非小细胞肺癌(NSCLC)的有效性和安全性，选择KRAS野生型肿瘤患者排除那些最不可能的患者，同时增加那些最有可能从治疗中受益的患者。虽然观察到的应答率很低，但一些患者经历了长期的疾病控制，同时肺癌症状迅速而持久地缓解，这表明达科米尼对KRAS野生型NSCLC具有相关的活性。
This phase 2 trial (ClinicalTrials.gov identifier NCT00548093) assessed the efficacy, safety, and impact on health‐related quality of life of dacomitinib (PF‐00299804), an irreversible tyrosine kinase inhibitor (TKI) of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, in patients with KRAS wild‐type non–small cell lung cancer (NSCLC). Patients with advanced NSCLC, progression on 1 or 2 regimens of chemotherapy and erlotinib, KRAS wild‐type or known EGFR‐sensitizing mutant tumor, and Eastern Cooperative Oncology Group performance status of 0 to 2 received 45 mg of dacomitinib once daily continuously in 21‐day cycles. A total of 66 patients enrolled (adenocarcinoma, n = 50; those without adenocarcinoma [nonadenocarcinoma], n = 16). The objective response rate (ORR) for patients with adenocarcinoma (primary endpoint) was 5% (2 partial responses; 1‐sided P = .372 for null hypothesis [H0]: ORR ≤ 5%) and 6% (1 partial response) for patients with nonadenocarcinoma. Responders included: 2 of 25 EGFR mutation‐positive tumors; 1 of 3 EGFR wild‐type with HER2 amplification. Median progression‐free survival was 12 weeks overall (n = 66) and 18 weeks (n = 26) for patients with EGFR mutation‐positive tumors. Common treatment‐related adverse events were of grade 1 or 2 severity, manageable with standard supportive care, and included diarrhea (grade 3 [G3], 12%), acneiform dermatitis (G3, 6%), exfoliative rash (G3, 3%), dry skin (G3, 0%), fatigue (G3, 3%), and stomatitis (G3, 2%). Six patients (9%) discontinued due to treatment‐related adverse events. By patient report, NSCLC symptoms of dyspnea, cough, and pain (chest, arm/shoulder) showed improvement first observed after 3 weeks on therapy. Dacomitinib demonstrated preliminary activity and acceptable tolerability in heavily pretreated patients, and may offer benefit in molecularly defined patient subsets. Cancer 2014;120:1145–1154. © 2014 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This study investigated the efficacy and safety of dacomitinib in advanced, refractory non–small cell lung cancer (NSCLC), selecting for patients with KRAS wild‐type tumors to exclude those least likely, and simultaneously enrich for those most likely, to benefit from therapy. Although the observed response rate was low, a number of patients experienced prolonged disease control accompanied by rapid and durable lung cancer symptom relief, suggesting that dacomitinib has relevant activity against KRAS wild‐type NSCLC.
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DOI：
10.1200/jco.2010.29.3126
发表时间：
2010-10-01
期刊：
Journal of clinical oncology : official journal of the American Society of Clinical Oncology
影响因子：
--
作者：
Kelly RJ;Carter C;Giaccone G
通讯作者：
Giaccone G
影响因子：
45.3
作者：
Roberts, Patrick J.;Stinchcombe, Thomas E.;Socinski, Mark A.
通讯作者：
Socinski, Mark A.
DOI：
10.1158/1078-0432.ccr-10-2571
发表时间：
2011-09-01
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Oxnard GR;Arcila ME;Chmielecki J;Ladanyi M;Miller VA;Pao W
通讯作者：
Pao W
影响因子：
8.4
作者：
BERGMAN, B;AARONSON, NK;SULLIVAN, M
通讯作者：
SULLIVAN, M
影响因子：
5.7
作者：
Gonzales, Andrea J.;Hook, Kenneth E.;Vincent, Patrick W.
通讯作者：
Vincent, Patrick W.