脑转移、EGFR 突变亚型和 EGFR-TKI 的产生共同影响 EGFR 突变型 NSCLC 患者的治疗结局。

Brain metastasis, EGFR mutation subtype and generation of EGFR-TKI jointly influence the treatment outcome of patient with EGFR-mutant NSCLC.

机构信息

Division of Thoracic Oncology, Department of Thoracic Medicine, College of Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan City, Taiwan.

Thoracic Oncology Unit, Chang Gung Memorial Hospital Cancer Center, Taoyuan City, Taiwan.

出版信息

Sci Rep. 2023 Nov 21;13(1):20323. doi: 10.1038/s41598-023-45815-8.

DOI:10.1038/s41598-023-45815-8

PMID:37989860

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10663477/

Abstract

Non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) mutation is brain metastasis (BM)-prone. We determined the impact of this hallmark, along with EGFR subtype and generation of tyrosine kinase inhibitor (TKI) treatment, on patients' outcome. 553 metastatic EGFR-mutant NSCLC patients received front-line EGFR-TKI treatment. Progression-free survival (PFS), overall survival (OS) and secondary T790M rate were analysed. BM was observed in 211 (38.2%) patients. BM (HR 1.20 [95% CI 0.99-1.48]; p = 0.053), ECOG PS 0-1 (HR 0.71 [95% CI 0.54-0.93]; p = 0.014) and afatinib treatment (HR 0.81 [95% CI 0.66-0.99]; p = 0.045) were associated with PFS. Afatinib-treated patients without BM demonstrated a significantly longer PFS (16.3 months) compared to afatinib-treated patients with BM (13.7 months) and to gefitinib/erlotinib-treated patients with (11.1 months) or without BM (14.2 months; p < 0.001). CNS-only progression trended higher in afatinib-treated patients. ECOG PS 0-1 (HR 0.41 [95% CI 0.31-0.56]; p < 0.001) and EGFR L858R mutation (HR 1.46 [95% CI 1.13-1.88]; p = 0.003), but not BM, were the predictors for OS. BM (OR 2.02 [95% CI 1.02-4.08]; p = 0.040), afatinib treatment (OR 0.26 [95% CI 0.12-0.50]; p < 0.001) and EGFR L858R mutation (OR 0.55 [95% CI 0.28-1.05]; p = 0.070) were associated with secondary T790M rate. In BM patients, gefitinib/erlotinib-treated ones with 19 deletion mutation and afatinib-treated ones with L858R mutation had the highest and the lowest T790M rate (94.4% vs. 27.3%, p < 0.001), respectively. BM and generation of EGFR-TKI jointly impact PFS and secondary T790M rate in patients with EGFR-mutant NSCLC, whereas OS was mainly associated with EGFR subtype.

摘要

非小细胞肺癌（NSCLC）伴表皮生长因子受体（EGFR）突变易发生脑转移（BM）。我们确定了这一特征，以及 EGFR 亚型和酪氨酸激酶抑制剂（TKI）治疗的产生，对患者结局的影响。553 例转移性 EGFR 突变 NSCLC 患者接受一线 EGFR-TKI 治疗。分析无进展生存期（PFS）、总生存期（OS）和继发 T790M 率。211 例（38.2%）患者出现 BM。BM（HR 1.20 [95% CI 0.99-1.48]；p=0.053）、ECOG PS 0-1（HR 0.71 [95% CI 0.54-0.93]；p=0.014）和阿法替尼治疗（HR 0.81 [95% CI 0.66-0.99]；p=0.045）与 PFS 相关。未发生 BM 的阿法替尼治疗患者的 PFS 明显长于发生 BM 的阿法替尼治疗患者（16.3 个月）和发生 BM 的吉非替尼/厄洛替尼治疗患者（11.1 个月）或未发生 BM 的吉非替尼/厄洛替尼治疗患者（14.2 个月；p<0.001）。阿法替尼治疗患者的中枢神经系统进展趋势更高。ECOG PS 0-1（HR 0.41 [95% CI 0.31-0.56]；p<0.001）和 EGFR L858R 突变（HR 1.46 [95% CI 1.13-1.88]；p=0.003）是 OS 的预测因素，但不是 BM。BM（OR 2.02 [95% CI 1.02-4.08]；p=0.040）、阿法替尼治疗（OR 0.26 [95% CI 0.12-0.50]；p<0.001）和 EGFR L858R 突变（OR 0.55 [95% CI 0.28-1.05]；p=0.070）与继发 T790M 率相关。在 BM 患者中，吉非替尼/厄洛替尼治疗的 19 缺失突变患者和阿法替尼治疗的 L858R 突变患者的 T790M 率最高（94.4% vs. 27.3%，p<0.001）和最低（分别）。BM 和 EGFR-TKI 的产生共同影响 EGFR 突变 NSCLC 患者的 PFS 和继发 T790M 率，而 OS 主要与 EGFR 亚型相关。