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标准剂量奥希替尼治疗伴有脑膜疾病的表皮生长因子受体突变型非小细胞肺腺癌。

Standard-Dose Osimertinib in EGFR-Mutated Non-Small-Cell Lung Adenocarcinoma With Leptomeningeal Disease.

机构信息

Department of Medical Oncology, Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia.

Department of Medical Oncology, Ballarat Health Services, Ballarat, Victoria, Australia.

出版信息

JCO Precis Oncol. 2021 Nov;5:561-568. doi: 10.1200/PO.20.00464.

Abstract

PURPOSE

Leptomeningeal disease (LMD) in epidermal growth factor receptor (EGFR)-mutant lung adenocarcinoma is associated with a poor prognosis and limited treatment options. Osimertinib is a potent third-generation EGFR tyrosine kinase inhibitor with confirmed CNS penetration. This study reports on outcomes of patients with EGFR-mutated non-small-cell lung cancer who developed LMD and were subsequently treated with osimertinib.

METHODS

We identified patients treated with osimertinib 80 mg PO daily under a compassionate access scheme across nine tertiary Australian institutes between July 2017 and July 2020. Patient demographics, tumor characteristics, and treatment history were collected. Median overall survival, median progression-free survival, disease control rates (DCR), and overall response rates (ORR) were assessed. Kaplan-Meier analysis was performed and descriptive statistics were used.

RESULTS

Thirty-nine patients were analyzed of which 74% were female. Exon 19 deletions (49%) and L858R point mutations (41%) were the most common EGFR mutations. Forty-nine percentage of patients were Eastern Cooperative Oncology Group 1. The median duration of osimertinib therapy was 6 months. The extracranial DCR and ORR were 60% and 54%, and the intracranial DCR and ORR were 68% and 53%, respectively. Median overall survival was 10.5 months (95% CI, 8.17 to 15.05 months).

CONCLUSION

There are limited treatment options for LMD in EGFR-positive lung cancer, and osimertinib at a dose of 80 mg daily is an active therapeutic option for these patients.

摘要

目的

表皮生长因子受体(EGFR)突变型肺腺癌中的脑膜疾病(LMD)与预后不良和有限的治疗选择相关。奥希替尼是一种有效的第三代 EGFR 酪氨酸激酶抑制剂,已证实具有中枢神经系统穿透力。本研究报告了在接受奥希替尼治疗的 EGFR 突变型非小细胞肺癌患者中出现 LMD 并随后接受奥希替尼治疗的患者的结果。

方法

我们在 2017 年 7 月至 2020 年 7 月期间,从澳大利亚 9 家三级医院通过同情准入计划,确定了每日口服 80mg 奥希替尼治疗的患者。收集了患者的人口统计学、肿瘤特征和治疗史。评估了中位总生存期、中位无进展生存期、疾病控制率(DCR)和总缓解率(ORR)。进行了 Kaplan-Meier 分析和描述性统计。

结果

分析了 39 例患者,其中 74%为女性。最常见的 EGFR 突变是外显子 19 缺失(49%)和 L858R 点突变(41%)。49%的患者为东部合作肿瘤学组 1 级。奥希替尼治疗的中位持续时间为 6 个月。颅外 DCR 和 ORR 分别为 60%和 54%,颅内 DCR 和 ORR 分别为 68%和 53%。中位总生存期为 10.5 个月(95%CI,8.17 至 15.05 个月)。

结论

EGFR 阳性肺癌的 LMD 治疗选择有限,奥希替尼 80mg 每日剂量是这些患者的有效治疗选择。

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