Dept of Medical Oncology, Catalan Institute of Oncology, Hospital Universitari Dr. Josep Trueta, Girona, Spain.
Eur Respir J. 2011 Mar;37(3):624-31. doi: 10.1183/09031936.00195609. Epub 2010 Jul 1.
Median survival of patients with brain metastases from nonsmall cell lung cancer (NSCLC) is poor and more effective treatments are urgently needed. We have evaluated the efficacy of erlotinib in this setting and its association with activating mutations in the epidermal growth factor receptor (EGFR) gene. We retrospectively identified patients with NSCLC and brain metastases treated with erlotinib. EGFR mutations in exons 19 and 21 were analysed by direct sequencing. Efficacy and tolerability were compared according to EGFR mutational status. 69 NSCLC patients with brain metastases were identified, 17 of whom harboured EGFR mutations. Objective response rate in patients with EGFR mutations was 82.4%; no responses were observed in unselected patients (p<0.001). Median (95% CI) time to progression within the brain for patients harbouring EGFR mutations was 11.7 (7.9-15.5) months, compared to 5.8 (5.2-6.4) months for control patients whose EGFR mutational status had not been assessed (p<0.05). Overall survival was 12.9 (6.2-19.7) months and 3.1 (2.5-3.9) months (p<0.001), respectively. The toxicity of erlotinib was as expected and no differences between cohorts were observed. Erlotinib is active in brain metastases from NSCLC; this clinical benefit is related to the presence of activating mutations in exons 19 or 21 of the EGFR gene.
非小细胞肺癌（NSCLC）脑转移患者的中位生存期较差，迫切需要更有效的治疗方法。我们评估了厄洛替尼在这种情况下的疗效及其与表皮生长因子受体（EGFR）基因激活突变的关系。我们回顾性地确定了接受厄洛替尼治疗的 NSCLC 和脑转移患者。通过直接测序分析外显子 19 和 21 中的 EGFR 突变。根据 EGFR 突变状态比较疗效和耐受性。确定了 69 例 NSCLC 伴脑转移患者，其中 17 例携带 EGFR 突变。携带 EGFR 突变的患者客观缓解率为 82.4％；未选择的患者未观察到反应（p<0.001）。携带 EGFR 突变的患者脑内进展的中位（95％CI）时间为 11.7（7.9-15.5）个月，而未评估 EGFR 突变状态的对照组患者为 5.8（5.2-6.4）个月（p<0.05）。总生存期分别为 12.9（6.2-19.7）个月和 3.1（2.5-3.9）个月（p<0.001）。厄洛替尼的毒性与预期相符，两组之间未观察到差异。厄洛替尼对 NSCLC 脑转移有效；这种临床获益与 EGFR 基因外显子 19 或 21 中的激活突变有关。
