JCO：Dacomitinib胜过厄洛替尼？

新一代EGFR衍生物 LUX-Lung 3期测试更为了HER家族各种因素衍生物畸替尼与标准中风在未经疗法的中叶EGFR变异HIV的非小细胞癌症（NSCLC）患儿当中的功效。畸替尼和“新一代EGFR衍生物”同可逆的、特异的EGFR酪氨酸还原酶衍生物（比如埃罗替尼和吉非替尼）相比，是否并不需要给予格外总体的诊疗益处呢？ 研究成果摘要 Ramalingam及其同事组织起来了一项2期随机测试，在拒绝接受过EGFR衍生物首次疗法的中叶NSCLC患儿当中必要更为dacomitinib和厄洛替尼，该研究成果同北美的以外不具有EGFR变异活性的患儿总体特别。（J Clin Oncol. 2012;30:3337-3344） 该研究成果纳入了188由此可知拒绝接受过非EGFR靶向疗法的中风的患儿。除了较宽体力状态低分2（dacomitinib四组19由此可知，厄洛替尼四组3由此可知）、出现EGFR变异（dacomitinib四组19由此可知，厄洛替尼四组11由此可知）、拒绝接受过2两种中风方案的患儿总数（dacomitinib四组40由此可知，厄洛替尼四组29由此可知）主因外，两个测试四组较总体。所有研究成果单纯按1:1随机分四组，分别施打dacomitinib 45mg/日或厄洛替尼15mg/日。该研究成果的主要绕道是无的发展生存期（PFS）。 多个测试常量看出dacomitinib格外有战术上。此番不下分别为17.0 vs 5.3%（P=0.011），诊疗获益混合病情稳定超过24周的客观此番不下分别为29.4% vs 14.9%（P=0.014），同时，dacomitinib四组的此番持续时间也格外有战术上（16.6月初 vs 9.2月初）。Dacomitinib 四组的PFS有统计学战术上（当中位PFS，29.月初 vs 1.9月初；HR，0.66；P=0.012）。关键性的是，几乎在所有诊疗和水分子亚型当中看出PFS获益，仅限于KRAS变异HIV患儿（当中位PFS,3.7月初 vs 1.9月初;HR,0.55;P=0.006），KRAS和EGFR野生型（当中位PFS,2.2月初 vs 1.8月初;HR,0.61;P=0.043），EGFR变异HIV患儿（虽然两四组当中位PFS仅有为7.4月初，但是HR为0.46格外利于dacomitinib四组，P=0.098）。两四组的总生存期（OS）无统计学总体差异，但是dacomitinib四组的当中位OS较厄洛替尼四组长2个月初（9.5月初 vs 7.4月初;HR,0.80;P=0.205）。 面对的过关斩将主要是dacomitinib四组较高的毒性反应会，仅限于腹泻（73% vs 48%），痤疮；也皮炎（64% vs 57%），口腔炎（29% vs 11%），甲沟炎（26% vs 8%），和其他不常见的类用药。另外，Dacomitinib四组需要减小mg（41% vs 17%）的患儿和停药（7由此可知 vs 2由此可知）的患儿大多。 卫报 如果dacomitinib的毒性反应会可被增加的话将是癌症的希望。事实上，该用药在广泛的NSCLC人群当中要比起厄洛替尼，特别是在是在KRAS变异和/或EGFR野生型患儿当中，这证明dacomitinib或许会使一个值得注意的疗法选项。我们期待正在透过的研究成果dacomitinib 和厄洛替尼的3期随机随机对照测试的结果，在它视作拒绝接受过疗法的中叶NSCLC患儿姑息疗法的一个有效选项在此之后，对于诊疗医师来说学习如何管理制度该用药的类用药是很关键性的。与厄洛替尼特别的扩大阅读：JCO：Dacomitinib比起厄洛替尼？厄洛替尼缩短非小细胞癌症患儿中风时间【ASCO 2012】厄洛替尼专用疗法使EGFR变异NSCLC患儿获益厄洛替尼专用疗法可使EGFR变异NSCLC患儿得益于EGFR变异指导工作厄洛替尼疗法中叶癌症格外多信息请点击：有关厄洛替尼格外多网际网路Randomized Phase II Study of Dacomitinib (PF-00299804), an Irreversible Pan–Human Epidermal Growth Factor Receptor Inhibitor, Versus Erlotinib in Patients With Advanced Non–Small-Cell Lung CancerPurpose This randomized, open-label trial compared dacomitinib (PF-00299804), an irreversible inhibitor of human epidermal growth factor receptors (EGFR)/HER1, HER2, and HER4, with erlotinib, a reversible EGFR inhibitor, in patients with advanced non–small-cell lung cancer (NSCLC).Patients and Methods Patients with NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, no prior HER-directed therapy, and one/two prior chemotherapy regimens received dacomitinib 45 mg or erlotinib 150 mg once daily.Results One hundred eighty-eight patients were randomly assigned. Treatment arms were balanced for most clinical and molecular characteristics. Median progression-free survival (PFS; primary end point) was 2.86 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (hazard ratio [HR] = 0.66; 95% CI, 0.47 to 0.91; two-sided P = .012); in patients with KRAS wild-type tumors, median PFS was 3.71 months for patients treated with dacomitinib and 1.91 months for patients treated with erlotinib (HR = 0.55; 95% CI, 0.35 to 0.85; two-sided P = .006); and in patients with KRAS wild-type/EGFR wild-type tumors, median PFS was 2.21 months for patients treated with dacomitinib and 1.84 months for patients treated with erlotinib (HR = 0.61; 95% CI, 0.37 to 0.99; two-sided P = .043). Median overall survival was 9.53 months for patients treated with dacomitinib and 7.44 months for patients treated with erlotinib (HR = 0.80; 95% CI, 0.56 to 1.13; two-sided P = .205). Adverse event-related discontinuations were uncommon in both arms. Common treatment-related adverse events were dermatologic and gastrointestinal, predominantly grade 1 to 2, and more frequent with dacomitinib.Conclusion Dacomitinib demonstrated significantly improved PFS versus erlotinib, with acceptable toxicity. PFS benefit was observed in most clinical and molecular subsets, notably KRAS wild-type/EGFR any status, KRAS wild-type/EGFR wild-type, and EGFR mutants.