三代高剂量 EGFR 酪氨酸激酶抑制剂治疗 EGFR 突变型非小细胞肺癌伴脑膜转移患者的疗效。
Effectiveness of high-dose third-generation EGFR-tyrosine kinase inhibitors in treating EGFR-mutated non-small cell lung cancer patients with leptomeningeal metastasis.
机构信息
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China; Wenzhou Medical University, Postgraduate Training Base Alliance, Wenzhou 325000, China.
Zhejiang Cancer Hospital, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China; Department of Thoracic Medical Oncology, Zhejiang Cancer Hospital, Hangzhou 310022, China; Department of Oncology, The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China.
出版信息
Lung Cancer. 2024 Feb;188:107475. doi: 10.1016/j.lungcan.2024.107475. Epub 2024 Jan 20.
BACKGROUND
Leptomeningeal metastasis (LM) is associated with an extremely poor prognosis in patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC). The third-generation EGFR-tyrosine kinase inhibitors (TKIs), currently the preferred drug of choice, have significantly improved treatment outcomes in these patients. However, the optimal dose of third-generation EGFR-TKIs for clinical use remains undetermined in NSCLC patients with LM.
METHODS
We retrospectively analyzed the clinical characteristics and treatment outcomes of 105 patients with EGFR-mutated NSCLC and cytologically confirmed LM who had received third-generation EGFR-TKI treatment after LM diagnosis. Patients were stratified into high- and standard-dose groups based on the treatment dose of third-generation EGFR-TKI. Subsequent treatments for LM were collected, particularly the efficacy of different doses of third-generation EGFR-targeted drugs.
RESULTS
The median follow-up period was 28.7 months (range 0.6-40.2) at the cut-off date of August 27, 2023. The 105 included patients who received third-generation EGFR-TKI treatment had a clinical response rate (CRR) of 54.3 % (57/105), and the median overall survival (OS) from LM diagnosis was 12.3 months (95 % confidence interval [CI] = 10.0-15.0). Among them, 46 (43.8 %) patients received a high-dose regimen, and the remaining 59 (56.2 %) patients were treated with standard-dose drugs. Patients treated with high-dose third-generation EGFR-TKIs showed a higher CRR and longer OS than those treated with standard-dose therapy (65.2 % vs. 45.8 %, p = 0.047; 15.0 vs. 10.2 months, p = 0.014). Importantly, high-dose third-generation EGFR-TKI showed superior OS than standard-dose treatment in all subgroups (prior first-/second-generation EGFR-TKI resistance group, 19.5 vs. 9.8 months, p = 0.047; third-generation EGFR-TKI resistance group, 10.0 vs. 4.3 months, p = 0.045; EGFR-TKI naive group, not reach vs. 15.6 months, p = 0.031). Multivariate analysis revealed that high-dose third-generation EGFR-TKIs, intrathecal chemotherapy, previous TKI treatment history, and Karnofsky Performance Status score were independent predictors of OS (all p < 0.05).
CONCLUSIONS
High-dose third-generation EGFR-TKIs are effective treatments for NSCLC patients with EGFR mutations and LM, regardless of previous EGFR-TKI exposure.
背景
脑膜转移（LM）与表皮生长因子受体（EGFR）突变的非小细胞肺癌（NSCLC）患者的预后极差。目前首选的第三代 EGFR-酪氨酸激酶抑制剂（TKI）显著改善了这些患者的治疗效果。然而，对于伴有 LM 的 NSCLC 患者，第三代 EGFR-TKI 的最佳临床剂量仍未确定。
方法
我们回顾性分析了 105 例 EGFR 突变的 NSCLC 患者的临床特征和治疗结果，这些患者在 LM 诊断后接受了第三代 EGFR-TKI 治疗，且 LM 经细胞学证实。根据第三代 EGFR-TKI 的治疗剂量，将患者分为高剂量组和标准剂量组。收集后续针对 LM 的治疗情况，特别是不同剂量第三代 EGFR 靶向药物的疗效。
结果
截至 2023 年 8 月 27 日截止日期，中位随访时间为 28.7 个月（范围 0.6-40.2）。105 例接受第三代 EGFR-TKI 治疗的患者的临床缓解率（CRR）为 54.3%（57/105），从 LM 诊断开始的中位总生存期（OS）为 12.3 个月（95%置信区间[CI]为 10.0-15.0）。其中，46 例（43.8%）患者接受了高剂量方案，其余 59 例（56.2%）患者接受了标准剂量药物治疗。与标准剂量治疗相比，接受高剂量第三代 EGFR-TKI 治疗的患者具有更高的 CRR 和更长的 OS（65.2% vs. 45.8%，p=0.047；15.0 个月 vs. 10.2 个月，p=0.014）。重要的是，高剂量第三代 EGFR-TKI 在所有亚组中均显示出优于标准剂量治疗的 OS（既往第一代/第二代 EGFR-TKI 耐药组，19.5 个月 vs. 9.8 个月，p=0.047；第三代 EGFR-TKI 耐药组，10.0 个月 vs. 4.3 个月，p=0.045；EGFR-TKI 初治组，不可评估 vs. 15.6 个月，p=0.031）。多变量分析显示，高剂量第三代 EGFR-TKI、鞘内化疗、既往 TKI 治疗史和卡氏功能状态评分是 OS 的独立预测因素（均 p<0.05）。
结论
高剂量第三代 EGFR-TKI 是治疗伴有 EGFR 突变和 LM 的 NSCLC 患者的有效方法，无论患者之前是否接受过 EGFR-TKI 治疗。
Zotero 插件