Brazel Danielle, Smith Janellen, Ou Sai-Hong Ignatius, Nagasaka Misako
Department of Hematology/Oncology, Scripps Clinic/Scripps Green Hospital, La Jolla, CA, USA.
Chao Family Cancer Center, University of California Irvine School of Medicine, 101 The City Drive, Orange, CA, 92868, USA.
Target Oncol. 2025 Mar;20(2):235-245. doi: 10.1007/s11523-025-01128-6. Epub 2025 Feb 4.
Targeted therapies have revolutionized treatment of non-small-cell lung cancer (NSCLC); however, epidermal growth factor receptor (EGFR) exon20ins mutations are resistant to tyrosine kinase inhibitors. Amivantamab utilizes multiple mechanisms of action to bypass the altered binding site conformation and recruits immune cells for anti-cancer activity. Amivantamab is approved in the frontline setting of EGFR exon20ins-mutated NSCLC in combination with carboplatin plus pemetrexed. Single-agent amivantamab is approved in second line or later for EGFR exon20ins. Furthermore, amivantamab with lazertinib for first line as well as amivantamab in combination with carboplatin and pemetrexed for second line after osimertinib have both been approved in the treatment of NSCLC harboring EGFR-sensitizing mutations. Now with multiple indications, we must learn how to manage the unique side effects of amivantamab to maximize treatment benefit for the patients. Side effects of amivantamab can be associated with inhibition of the EGFR and/or mesenchymal epithelial transcription factor (MET) signaling pathways. This work reviews the mechanism of action, pharmacology, clinical trial data, and covers management of toxicities. This guide is designed as a practical reference tool for clinicians, pharmacists, and basic science researchers.
靶向治疗彻底改变了非小细胞肺癌（NSCLC）的治疗方式；然而，表皮生长因子受体（EGFR）外显子20插入突变对酪氨酸激酶抑制剂具有抗性。阿美替尼利用多种作用机制绕过改变的结合位点构象，并募集免疫细胞以发挥抗癌活性。阿美替尼被批准用于EGFR外显子20插入突变的NSCLC一线治疗，与卡铂加培美曲塞联合使用。阿美替尼单药被批准用于EGFR外显子20插入突变的二线及以后治疗。此外，阿美替尼与拉泽替尼联合用于一线治疗，以及阿美替尼与卡铂和培美曲塞联合用于奥希替尼后的二线治疗，均已被批准用于治疗携带EGFR敏感突变的NSCLC。现在有了多种适应症，我们必须学会如何管理阿美替尼独特的副作用，以最大限度地为患者带来治疗益处。阿美替尼的副作用可能与EGFR和/或间充质上皮转化因子（MET）信号通路的抑制有关。这项工作回顾了其作用机制、药理学、临床试验数据，并涵盖了毒性管理。本指南旨在为临床医生、药剂师和基础科学研究人员提供实用的参考工具。
