文章：

奥希替尼在表皮生长因子受体突变型非小细胞肺癌早期及局部晚期治疗中的应用：现有证据与未来展望

Osimertinib in the Treatment of Epidermal Growth Factor Receptor-Mutant Early and Locally Advanced Stages of Non-Small-Cell Lung Cancer: Current Evidence and Future Perspectives

原文发布日期：16 February 2025

DOI: 10.3390/cancers17040668

类型: Article

开放获取: 是

英文摘要：

The treatment of epidermal growth factor receptor (EGFR)-mutant non-small-cell lung cancer (NSCLC) patients was dramatically revolutionized by the introduction of EGFR tyrosine kinase inhibitors in clinical practice, both in advanced and locally advanced/early stages. The present work focuses on osimertinib use in locally advanced and early NSCLC stages. Phase 3 clinical trials have supported the use of osimertinib as the new standard of care, both in the adjuvant setting and in locally advanced disease. The ADAURA study reported an overall survival (OS) advantage for adjuvant osimertinib in completely resected stage II-IIIA EGFR-mutant tumors, while the LAURA study proved a statistically significant benefit in progression-free survival (PFS) and a delay of central nervous system metastasis development in EGFR-mutant patients treated with osimertinib maintenance after concurrent chemoradiotherapy for locally advanced disease. In the neoadjuvant setting, data on osimertinib’s efficacy are conflicting; therefore, the Neo-ADAURA study is evaluating the efficacy and safety of neoadjuvant osimertinib alone or in combination with chemotherapy in patients with stage II-IIIB NSCLC and common EGFR mutations. We discuss several issues that need to be clarified, such as the efficacy of the drug on uncommon mutations, the long-term impact on survival, and the management of resistance mechanisms. Moreover, we report the studies that are trying to identify potential biomarkers of response, such as the circulating tumor DNA (ctDNA), with the aim of selecting patients who will benefit most from osimertinib.

摘要翻译： 

表皮生长因子受体（EGFR）突变非小细胞肺癌（NSCLC）的治疗，因EGFR酪氨酸激酶抑制剂在临床实践中的应用——无论是在晚期还是局部晚期/早期阶段——发生了革命性变化。本文聚焦于奥希替尼在局部晚期及早期NSCLC阶段的应用。三期临床试验已支持将奥希替尼作为新标准治疗，既适用于辅助治疗，也适用于局部晚期疾病。ADAURA研究报道了奥希替尼辅助治疗在完全切除的II-IIIA期EGFR突变肿瘤中具有总生存期（OS）优势；而LAURA研究则证实，对于局部晚期疾病接受同步放化疗后采用奥希替尼维持治疗的EGFR突变患者，其无进展生存期（PFS）具有统计学显著获益，并延缓了中枢神经系统转移的发生。在新辅助治疗方面，关于奥希替尼疗效的数据存在矛盾；因此，Neo-ADAURA研究正在评估奥希替尼单药或联合化疗作为新辅助治疗，在II-IIIB期NSCLC及常见EGFR突变患者中的疗效和安全性。我们讨论了若干需澄清的问题，例如该药物对罕见突变的疗效、对生存期的长期影响以及耐药机制的管理。此外，我们报告了旨在识别潜在疗效生物标志物（如循环肿瘤DNA）的研究，以期筛选出最能从奥希替尼治疗中获益的患者。

原文链接：

Osimertinib in the Treatment of Epidermal Growth Factor Receptor-Mutant Early and Locally Advanced Stages of Non-Small-Cell Lung Cancer: Current Evidence and Future Perspectives