High-dose third-generation EGFR-TKIs combined with intrathecal pemetrexed in advanced EGFR-mutant NSCLC with leptomeningeal metastases following EGFR-TKI therapy.

IF 3.4 2区 医学 Q2 ONCOLOGY
Shugui Wu, Zhengang Qiu, Huaqiu Shi, Wei Yu, Linfang Liu, Longqiu Wu, Wenjuan Zhong
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引用次数: 0

Abstract

Background: Leptomeningeal metastasis in EGFR-mutant (EGFRm) non-small-cell lung cancer (NSCLC) is a severe complication particularly prevalent in patients who have previously been treated with EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, an optimal treatment strategy for dealing with leptomeningeal metastases in patients with NSCLC has yet to be developed. High-dose EGFR-TKIs in combination with intrathecal chemotherapy may offer a promising treatment strategy for this patient population.

Methods: We retrospectively identified patients with EGFRm NSCLC who were diagnosed at the First Affiliated Hospital of Gannan Medical University between January 1, 2018, and December 31, 2023. All patients developed leptomeningeal metastases after EGFR-TKI treatment and then received intrathecal pemetrexed chemotherapy in combination with high-dose third-generation EGFR-TKIs (osimertinib 160 mg/day, furmonertinib 160 mg/day, or aumolertinib 165 mg/day), with or without other therapies. Intracranial response, intracranial progression-free survival, overall survival, and safety were evaluated.

Results: Twenty-three patients were enrolled. The median follow-up was 20 months (range, 2-35). The median number of intrathecal pemetrexed injections was 4 (range, 2-26). The intracranial symptom relief rate was 91.3% (21/23), intracranial disease control rate was 86.96% (20/23), median intracranial progression-free survival was 10 months (95% CI, 1.52-18.48), and median overall survival was 12 months (95% CI, 5.43-18.57). The most frequent adverse event was myelosuppression (n = 10, 43.48%), which was limited to grade 1 or 2. Two grade 3 adverse events were observed, including one case of interstitial pneumonia and one case of diarrhea. Univariate and multivariate analyses demonstrated that the combination of bevacizumab and an Eastern Cooperative Oncology Group performance status of ≤ 1 were favorable prognostic factors for survival.

Conclusions: High-dose third-generation EGFR-TKIs combined with pemetrexed intrathecal chemotherapy demonstrated a high rate of intracranial symptom relief and manageable safety in patients with EGFRm NSCLC who developed leptomeningeal metastases after previous EGFR-TKI therapy.

高剂量第三代EGFR-TKI联合鞘内培美曲塞治疗EGFR-TKI治疗后发生轻脑膜转移的晚期egfr突变NSCLC。
背景:egfr突变体(EGFRm)非小细胞肺癌(NSCLC)的轻脑膜转移是一种严重的并发症,尤其在先前接受过egfr -酪氨酸激酶抑制剂(EGFR-TKIs)治疗的患者中普遍存在。然而,治疗非小细胞肺癌患者脑脊膜轻脑膜转移的最佳治疗策略尚未开发。高剂量EGFR-TKIs联合鞘内化疗可能为这类患者提供一种有希望的治疗策略。方法:回顾性分析2018年1月1日至2023年12月31日在甘南医科大学第一附属医院诊断的EGFRm NSCLC患者。所有患者在接受EGFR-TKI治疗后均出现脑膜转移,然后接受鞘内培美曲塞化疗联合高剂量第三代EGFR-TKI(奥西替尼160 mg/天、呋莫替尼160 mg/天或奥莫替尼165 mg/天),联合或不联合其他治疗。评估颅内反应、颅内无进展生存期、总生存期和安全性。结果:23例患者入组。中位随访时间为20个月(范围2-35)。鞘内培美曲塞注射的中位数为4次(范围2-26次)。颅内症状缓解率为91.3%(21/23),颅内疾病控制率为86.96%(20/23),中位颅内无进展生存期为10个月(95% CI, 1.52-18.48),中位总生存期为12个月(95% CI, 5.43-18.57)。最常见的不良事件是骨髓抑制(n = 10, 43.48%),仅限于1级或2级。观察到2例3级不良事件,包括1例间质性肺炎和1例腹泻。单因素和多因素分析表明,贝伐单抗联合治疗和东部肿瘤合作组的表现状态≤1是有利于生存的预后因素。结论:大剂量第三代EGFR-TKIs联合培美曲塞鞘内化疗对EGFR-TKI治疗后发生脑膜轻转移的NSCLC患者颅内症状缓解率高,安全性可管理。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
BMC Cancer
BMC Cancer 医学-肿瘤学
CiteScore
6.00
自引率
2.60%
发文量
1204
审稿时长
6.8 months
期刊介绍: BMC Cancer is an open access, peer-reviewed journal that considers articles on all aspects of cancer research, including the pathophysiology, prevention, diagnosis and treatment of cancers. The journal welcomes submissions concerning molecular and cellular biology, genetics, epidemiology, and clinical trials.
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