Lowe Center for Thoracic Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA.
Clin Cancer Res. 2010 Dec 1;16(23):5873-82. doi: 10.1158/1078-0432.CCR-10-1588. Epub 2010 Oct 28.
Gefitinib and erlotinib can penetrate into the central nervous system (CNS) and elicit responses in patients with brain metastases (BM) from non-small cell lung cancer (NSCLC). However, there are incomplete data about their impact on the development and control of CNS metastases.
Patients with stage IIIB/IV NSCLC with somatic EGFR mutations initially treated with gefitinib or erlotinib were identified. The cumulative risk of CNS progression was calculated using death as a competing risk.
Of the 100 patients, 19 had BM at the time of diagnosis of advanced NSCLC; 17 of them received CNS therapy before initiating gefitinib or erlotinib. Eighty-four patients progressed after a median potential follow-up of 42.2 months. The median time to progression was 13.1 months. Twenty-eight patients developed CNS progression, 8 of whom had previously treated BM. The 1- and 2-year actuarial risk of CNS progression was 7% and 19%, respectively. Patient age and EGFR mutation genotype were significant predictors of the development of CNS progression. The median overall survival for the entire cohort was 33.1 months.
Our data suggest a lower risk of CNS progression in patients with advanced NSCLC and somatic EGFR mutations initially treated with gefitinib or erlotinib than published rates of 40% in historical series of advanced NSCLC patients. Further research is needed to distinguish between the underlying rates of developing CNS metastases between NSCLC with and without EGFR mutations and the impact of gefitinib and erlotinib versus chemotherapy on CNS failure patterns in these patients.
吉非替尼和厄洛替尼可穿透中枢神经系统（CNS），并在非小细胞肺癌（NSCLC）脑转移（BM）患者中引发反应。然而，关于它们对 CNS 转移的发展和控制的影响，仍存在不完全的数据。
确定了初始接受吉非替尼或厄洛替尼治疗的具有体细胞 EGFR 突变的 IIIB/IV 期 NSCLC 患者。使用死亡作为竞争风险来计算 CNS 进展的累积风险。
在 100 例患者中，有 19 例在诊断为晚期 NSCLC 时患有 BM；其中 17 例在开始使用吉非替尼或厄洛替尼之前接受了 CNS 治疗。84 例患者在中位潜在随访 42.2 个月后进展。中位无进展生存期为 13.1 个月。28 例患者发生 CNS 进展，其中 8 例先前有 BM 治疗史。1 年和 2 年的 CNS 进展实际风险分别为 7%和 19%。患者年龄和 EGFR 突变基因型是 CNS 进展的显著预测因素。整个队列的中位总生存期为 33.1 个月。
我们的数据表明，与晚期 NSCLC 患者的历史系列中报道的 40%的发生率相比，初始接受吉非替尼或厄洛替尼治疗的具有体细胞 EGFR 突变的晚期 NSCLC 患者发生 CNS 进展的风险较低。需要进一步的研究来区分 NSCLC 患者中有无 EGFR 突变的 CNS 转移的潜在发生率，以及吉非替尼和厄洛替尼与化疗对这些患者 CNS 失败模式的影响。
