Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer: a retrospective analysis of an MD Anderson Cancer Center phase I population.
Revisiting clinical trials using EGFR inhibitor-based regimens in patients with advanced non-small cell lung cancer: a retrospective analysis of an MD Anderson Cancer Center phase I population.
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DOI：
10.18632/oncotarget.1028
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发表时间：
2013-05
期刊：
影响因子：
--
通讯作者：
Kurzrock R
中科院分区：
文献类型：
--
作者：
Wheler J;Falchook G;Tsimberidou AM;Hong D;Naing A;Piha-Paul S;Chen SS;Heymach J;Fu S;Stephen B;Fok JY;Janku F;Kurzrock R
单药EGFR抑制剂治疗主要对肺癌和EGFR突变患者有效。治疗出现耐药性或从一开始就不敏感的患者，通常是因为耐药突变、其他异常或缺乏EGFR突变，可能需要合理的组合。因此，我们研究了以EGFR抑制剂为基础的联合方案在I期临床确诊的严重预治疗的非小细胞肺癌(NSCLC)患者中的结果。我们回顾了接受基于EGFR抑制剂的联合方案治疗的非小细胞肺癌患者的电子记录：厄洛替尼和西妥昔单抗；厄洛替尼、西妥昔单抗和贝伐单抗；厄洛替尼和达沙替尼；厄洛替尼和波特佐米；或西妥昔单抗和西罗莫司。有16%的患者检测到EGFR突变(21/131)。15例EGFR突变型非小细胞肺癌患者和24例EGFR野生型疾病患者接受了以EGFR抑制剂为基础的联合方案。20%的EGFR突变患者(3/15；2例对以前的厄洛替尼敏感和继发耐药，1例耐药突变)和26%(5/19)的野生型疾病患者获得了6个月的≥稳定/部分缓解(PR)。鳞状细胞组织学可评估的三名患者中有一名获得26.5个月的SD(EGFR野生型，TP53突变，方案=erlotinib，西妥昔单抗和贝伐单抗)。在34名可评估的晚期、难治性非小细胞肺癌患者中，有8名(24%)在以表皮生长因子受体抑制剂为基础的联合方案(埃洛替尼、西妥昔单抗、埃洛替尼、西妥昔单抗和贝伐单抗；以及埃洛替尼、波替佐米)中获得了6个月/PR(PR=3；SD≥6个月=5)，包括对单药表皮生长因子受体抑制剂、耐药突变、野生型疾病和鳞状组织学二次耐药的患者。
Single-agent EGFR inhibitor therapy is effective mainly in patients with lung cancer and EGFR mutations. Treating patients who develop resistance, or who are insensitive from the outset, often because of resistant mutations, other aberrations or the lack of an EGFR mutation, probably requires rational combinations. We therefore investigated the outcome of EGFR inhibitor-based combination regimens in patients with heavily-pretreated non-small cell lung cancer (NSCLC) referred to a Phase I Clinic. We reviewed the electronic records of patients with NSCLC treated with an EGFR inhibitor-based combination regimen: erlotinib and cetuximab; erlotinib, cetuximab and bevacizumab; erlotinib and dasatinib; erlotinib and bortezomib; or cetuximab and sirolimus. EGFR mutations were detected in 16% of patients (21/131). EGFR inhibitor-based combination regimens were administered to 15 patients with EGFR-mutant NSCLC and 24 with EGFR wild-type disease. Stable disease (SD) ≥6 months/partial remission (PR) was attained in 20% of EGFR-mutant patients (3/15; two with sensitive mutations and secondary resistance to prior erlotinib, and one with a resistant mutation), as well as 26% of evaluable patients (5/19) with wild-type disease. One of three evaluable patients with squamous cell histology achieved SD for 26.5 months (EGFR wild-type, TP53-mutant, regimen=erlotinib, cetuximab and bevacizumab). Eight of 34 evaluable patients (24%) with advanced, refractory NSCLC evaluable for response achieved SD ≥6 months/PR (PR=3; SD ≥6 months=5) on EGFR inhibitor-based combination regimens (erlotinib, cetuximab; erlotinib, cetuximab and bevacizumab; and, erlotinib, bortezomib), including patients with secondary resistance to single-agent EGFR inhibitors, resistant mutations, wild-type disease, and, squamous histology.
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影响因子：
158.5
作者：
Lynch, TJ;Bell, DW;Haber, DA
通讯作者：
Haber, DA
用PI3K/AKT/MTOR轴抑制剂治疗的晚期癌症患者的PIK3CA突变。
影响因子：
5.7
作者：
Janku F;Tsimberidou AM;Garrido-Laguna I;Wang X;Luthra R;Hong DS;Naing A;Falchook GS;Moroney JW;Piha-Paul SA;Wheler JJ;Moulder SL;Fu S;Kurzrock R
通讯作者：
Kurzrock R
影响因子：
5.7
作者：
Chaft JE;Arcila ME;Paik PK;Lau C;Riely GJ;Pietanza MC;Zakowski MF;Rusch V;Sima CS;Ladanyi M;Kris MG
通讯作者：
Kris MG
影响因子：
4.9
作者：
Mumenthaler SM;Foo J;Leder K;Choi NC;Agus DB;Pao W;Mallick P;Michor F
通讯作者：
Michor F
影响因子：
168.9
作者：
Pirker, Robert;Pereira, Jose R.;Hotko, Y.
通讯作者：
Hotko, Y.