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拉泽替尼作为表皮生长因子受体(EGFR)突变的局部晚期或转移性非小细胞肺癌(NSCLC)一线治疗的疗效和安全性的系统评价与荟萃分析

A Systematic Review and Meta-Analysis of the Efficacy and Safety of Lazertinib as First-Line Treatment for EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer (NSCLC).

作者信息

Jusni Louis Fabio Jonathan, Yonatan Eric Ricardo, Widjanarko Nicolas Daniel, Besri Rio Gusta Notario

机构信息

School of Medicine and Health Sciences, Atma Jaya Catholic University of Indonesia, Jakarta, Indonesia.

Fatima Hospital, Delta Pawan Subdistrict, Ketapang Regency, West Kalimantan, Indonesia.

出版信息

Hematol Oncol Stem Cell Ther. 2025 Jun 20. doi: 10.4103/hemoncstem.HEMONCSTEM-D-24-00041.

Abstract

BACKGROUND AND OBJECTIVE

Epidermal growth factor receptor (EGFR) mutations are a common driver of oncogenesis in non-small cell lung cancer (NSCLC). Lazertinib, a third-generation EGFR tyrosine kinase inhibitor (TKI), has shown promise as a first-line treatment for patients with locally advanced or metastatic EGFR-mutated NSCLC. However, the comparative efficacy and safety of lazertinib in this setting have not been thoroughly investigated. This study aims to evaluate the efficacy and safety of lazertinib for EGFR-mutated locally advanced NSCLC.

METHOD

This study was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We performed a search of PubMed, ProQuest, EBSCO, and ScienceDirect to identify eligible studies based on the PICOTS-SD criteria. The meta-analysis of overall survival (OS), progression-free survival (PFS), and adverse effects was performed using RevMan 5.4 software.

RESULTS

This review included a total of three randomized controlled trials. The pooled analysis revealed significant differences in PFS, with a hazard ratio (HR) of 0.44 (95% confidence interval [CI]: 0.37-0.53). However, OS showed no significant differences, with an HR of 0.82 (95% CI: 0.64-1.06). Paresthesia occurred significantly more frequently in the lazertinib group (odds ratio [OR]: 11.30; 95% CI: 7.30-17.49). In contrast, the incidence of diarrhea and increases in Alanine Transaminase (ALT) and Aspartate Aminotransferase (AST) levels were significantly higher in the gefitinib group, with ORs of 0.52 (95% CI: 0.39-0.70), 0.35 (95% CI: 0.25-0.50), and 0.32 (95% CI: 0.22-0.47), respectively.

CONCLUSION

Lazertinib demonstrated a greater therapeutic benefit for patients with EGFR-mutated advanced NSCLC compared to first-generation EGFR-TKIs. Further research is needed to validate these findings.

摘要

背景与目的

表皮生长因子受体(EGFR)突变是非小细胞肺癌(NSCLC)致癌的常见驱动因素。第三代EGFR酪氨酸激酶抑制剂(TKI)拉泽替尼已显示出有望作为局部晚期或转移性EGFR突变NSCLC患者的一线治疗药物。然而,拉泽替尼在此情况下的相对疗效和安全性尚未得到充分研究。本研究旨在评估拉泽替尼治疗EGFR突变的局部晚期NSCLC的疗效和安全性。

方法

本研究按照系统评价和Meta分析的首选报告项目指南进行。我们在PubMed、ProQuest、EBSCO和ScienceDirect上进行检索,以根据PICOTS-SD标准确定符合条件的研究。使用RevMan 5.4软件对总生存期(OS)、无进展生存期(PFS)和不良反应进行Meta分析。

结果

本综述共纳入三项随机对照试验。汇总分析显示PFS有显著差异,风险比(HR)为0.44(95%置信区间[CI]:0.37 - 0.53)。然而,OS无显著差异,HR为0.82(95%CI:0.64 - 1.06)。拉泽替尼组感觉异常的发生频率显著更高(优势比[OR]:11.30;95%CI:7.30 - 17.49)。相比之下,吉非替尼组腹泻的发生率以及丙氨酸转氨酶(ALT)和天冬氨酸转氨酶(AST)水平升高的发生率显著更高,OR分别为0.52(95%CI:0.39 - 0.70)、0.35(95%CI:0.25 - 0.50)和0.32(95%CI:0.22 - 0.47)。

结论

与第一代EGFR-TKIs相比,拉泽替尼对EGFR突变的晚期NSCLC患者显示出更大的治疗益处。需要进一步研究来验证这些发现。

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