Scripps Clinic/Scripps Green Hospital, La Jolla, USA.
University of California Irvine Department of Medicine, Orange, CA, USA.
Respir Res. 2023 Oct 25;24(1):256. doi: 10.1186/s12931-023-02558-4.
Non-small cell lung cancer (NSCLC) patients with sensitizing oncogenic driver mutations benefit from targeted therapies. Tyrosine kinase inhibitors are highly effective against classic sensitizing epidermal growth factor receptor (EGFR) mutations, such as exon 19 deletions and exon 21 L858R point mutations. Conversely, EGFR exon 20 insertions (exon20ins) are resistant to the traditional EGFR tyrosine kinase inhibitors (TKIs). In May 2021, the US Federal Drug Administration (FDA) provided accelerated approval to amivantamab (Rybrevant) in adults with locally advanced or metastatic NSCLC with EGFR exon20ins after treatment with platinum-based chemotherapy. Amivantamab was the first EGFR/MET bispecific antibody to be approved specifically for EGFR exon20ins where there was an unmet need. Furthermore, amivantamab is being evaluated in additional settings such as post osimertinib in sensitizing EGFR mutations as well as in MET altered NSCLC. Here we discuss amivantamab in regard to its mechanism of action, preclinical and clinical data, and clinical impact for patients with EGFR exon20ins NSCLC and beyond.
具有敏感致癌驱动突变的非小细胞肺癌（NSCLC）患者受益于靶向治疗。针对经典敏感表皮生长因子受体（EGFR）突变，如外显子 19 缺失和外显子 21 L858R 点突变，酪氨酸激酶抑制剂具有很高的疗效。相反，EGFR 外显子 20 插入（exon20ins）对传统的 EGFR 酪氨酸激酶抑制剂（TKIs）有耐药性。2021 年 5 月，美国食品和药物管理局（FDA）批准了 amivantamab（Rybrevant）用于铂类化疗后具有 EGFR exon20ins 的局部晚期或转移性 NSCLC 成人患者，这些患者之前接受过治疗。Amivantamab 是第一个专门针对 EGFR exon20ins 的 EGFR/MET 双特异性抗体，而 EGFR exon20ins 存在未满足的需求。此外，amivantamab 正在其他环境中进行评估，如在敏感 EGFR 突变后使用奥希替尼以及在 MET 改变的 NSCLC 中进行评估。在这里，我们将讨论 amivantamab 在其作用机制、临床前和临床数据以及对具有 EGFR exon20ins NSCLC 及其他疾病患者的临床影响方面的情况。
