Bian David J H, Lazaratos Anna-Maria, Maritan Sarah M, Quaiattini Andrea, Zeng Zhimin, Zhu Zhengfei, Sener Ugur, Malani Rachna, Kim Yu Jung, Ichihara Eiki, Cohen Victor, Rose April A N, Bouganim Nathaniel, Dankner Matthew
Faculty of Medicine, McGill University, Montreal, Quebec, Canada.
Rosalind and Morris Goodman Cancer Institute, Montreal, Quebec, Canada.
Heliyon. 2024 Apr 17;10(9):e29668. doi: 10.1016/j.heliyon.2024.e29668. eCollection 2024 May 15.
Leptomeningeal metastasis (LM) is a severe complication of non-small cell lung cancer (NSCLC). In patients with NSCLC LM harboring epidermal growth factor receptor () mutations, osimertinib is favored over alternative EGFR tyrosine kinase inhibitors (TKIs). However, the efficacy of osimertinib relative to other EGFR-TKIs is not well established for patients with LM. We aimed to compare the efficacy of EGFR-TKIs in mutated NSCLC LM.
This systematic review and meta-analysis performed according to PRISMA guidelines included studies of adult patients with -mutated NSCLC and a diagnosis of LM who received an EGFR-TKI for the treatment of LM. We searched Medline ALL, Embase, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science Core Collection. The evaluation of biases was done by using the Ottawa-Newscastle scale. The hazard ratio was used as the parameter of interest for overall survival (OS) and central nervous system-specific progression-free survival (PFS).
128 publications were included with 243 patients and 282 lines of EGFR-TKI for NSCLC LM that met inclusion criteria. The median PFS in patients receiving any EGFR-TKI was 9.1 months, and the median OS was 14.5 months. In univariate analyses of the entire cohort, osimertinib treatment demonstrated significantly prolonged PFS, but not OS, compared to other EGFR-TKIs. Osimertinib demonstrated significantly prolonged PFS and OS in the subset of patients who were previously treated with EGFR-TKIs, but not in EGFR-TKI naïve patients.
Osimertinib is associated with improved outcomes compared to other EGFR-TKIs, particularly in patients previously treated with EGFR-TKIs. An important limitation is that most patients were derived from retrospective reports. These results highlight the need for prospective studies for this difficult-to-treat patient population.
软脑膜转移（LM）是非小细胞肺癌（NSCLC）的一种严重并发症。在携带表皮生长因子受体（）突变的NSCLC-LM患者中，奥希替尼比其他表皮生长因子受体酪氨酸激酶抑制剂（TKIs）更受青睐。然而，对于LM患者，奥希替尼相对于其他表皮生长因子受体-TKIs的疗效尚未明确确立。我们旨在比较表皮生长因子受体-TKIs在突变型NSCLC-LM中的疗效。
本系统评价和荟萃分析按照PRISMA指南进行，纳入了成年携带突变型NSCLC且诊断为LM并接受表皮生长因子受体-TKI治疗LM的患者的研究。我们检索了Medline ALL、Embase、Cochrane对照试验中央注册库、Scopus和Web of Science核心合集。使用渥太华-纽卡斯尔量表进行偏倚评估。风险比用作总生存期（OS）和中枢神经系统特异性无进展生存期（PFS）的感兴趣参数。
纳入了128篇出版物，其中243例患者和282线用于NSCLC-LM的表皮生长因子受体-TKI符合纳入标准。接受任何表皮生长因子受体-TKI治疗的患者的中位PFS为9.1个月，中位OS为14.5个月。在整个队列的单因素分析中，与其他表皮生长因子受体-TKIs相比，奥希替尼治疗显示PFS显著延长，但OS未延长。在先前接受过表皮生长因子受体-TKIs治疗的患者亚组中，奥希替尼显示PFS和OS显著延长，但在未接受过表皮生长因子受体-TKIs治疗的患者中未显示。
与其他表皮生长因子受体-TKIs相比，奥希替尼与更好的预后相关，尤其是在先前接受过表皮生长因子受体-TKIs治疗的患者中。一个重要的局限性是大多数患者来自回顾性报告。这些结果凸显了对这一难以治疗的患者群体进行前瞻性研究的必要性。
