EGFR Exon 20 insertions in NSCLC: from biology to amivantamab, optimal treatment strategy and emerging therapeutics.

IF 2.6 4区 医学 Q2 ONCOLOGY
Future oncology Pub Date : 2025-10-01 Epub Date: 2025-08-22 DOI:10.1080/14796694.2025.2550927
Naoki Furuya
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引用次数: 0

Abstract

EGFR exon 20 insertion (Ex20ins) mutations are the third most frequent EGFR mutations, which accounts for around 4-12% of EGFR mutations in advanced NSCLC. It is well known that conventional EGFR-TKI monotherapy is less effective for patients with EGFR Ex20ins. Amivantamab is the first in class drug for established standard therapy of advanced stage NSCLC harboring Ex20ins mutations. Amivantamab has the following four unique mechanisms of action for Ex20ins mutated NSCLC; 1) dual-blocking receptor and inhibition of signaling pathway of EGFR and cMET, 2) antibody-dependent cellular cytotoxicity (ADCC) by NK cells, 3) antibody-dependent cellular trogocytosis (ADCT) by macrophages, 4) lysosomal receptor internalization and subsequent degradation. Amivantamab, in combination with carboplatin plus permetexed, was established in the PAPILLON study. However, it is unclear regarding the efficacy and CNS penetration of amivantamab for patients with Ex20ins mutations involving CNS/brain metastases. For patients with A763_Y764insFQEA mutation involving serious brain metastases, conventional EGFR-TKI might be an important treatment option. There are four phase III studies ongoing investigating new EGFR-TKI monotherapies or combination therapy with cytotoxic chemotherapy for EGFR Ex20ins mutations in the first-line setting. This review comprehensively summarized the biology and clinical characteristics of Ex20ins mutations and provide cutting-edge information and future perspectives.

EGFR外显子20在NSCLC中的插入:从生物学到阿米万他单抗,最佳治疗策略和新兴治疗方法。
EGFR外显子20插入(Ex20ins)突变是第三种最常见的EGFR突变,约占晚期NSCLC EGFR突变的4-12%。众所周知,传统的EGFR- tki单药治疗EGFR ex20in患者效果较差。Amivantamab是首个用于Ex20ins突变晚期NSCLC的标准治疗药物。阿米万他单抗对Ex20ins突变的NSCLC具有以下四种独特的作用机制:1)双阻断受体和EGFR和cMET信号通路的抑制,2)NK细胞的抗体依赖性细胞毒性(ADCC), 3)巨噬细胞的抗体依赖性细胞吞噬(ADCT), 4)溶酶体受体内化及其降解。阿米万他单抗联合卡铂+渗透,在PAPILLON研究中建立。然而,对于伴有中枢神经系统/脑转移的Ex20ins突变患者,阿米万他单抗的疗效和中枢神经系统的穿透性尚不清楚。对于A763_Y764insFQEA突变涉及严重脑转移的患者,传统的EGFR-TKI可能是一种重要的治疗选择。目前有四项III期研究正在调查一线EGFR Ex20ins突变的新的EGFR- tki单药或联合细胞毒性化疗。本文全面总结了Ex20ins突变的生物学和临床特征,并提供了最新的信息和未来的展望。
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
Future oncology
Future oncology ONCOLOGY-
CiteScore
5.40
自引率
3.00%
发文量
335
审稿时长
4-8 weeks
期刊介绍: Future Oncology (ISSN 1479-6694) provides a forum for a new era of cancer care. The journal focuses on the most important advances and highlights their relevance in the clinical setting. Furthermore, Future Oncology delivers essential information in concise, at-a-glance article formats - vital in delivering information to an increasingly time-constrained community. The journal takes a forward-looking stance toward the scientific and clinical issues, together with the economic and policy issues that confront us in this new era of cancer care. The journal includes literature awareness such as the latest developments in radiotherapy and immunotherapy, concise commentary and analysis, and full review articles all of which provide key findings, translational to the clinical setting.
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