# Advances in Targeted Therapy for Advanced Non-small Cell Lung Cancer with HER2 Mutation

## TL;DR

This paper reviews the current state and future directions of HER2-targeted therapies for advanced non-small cell lung cancer, focusing on drug development and treatment strategies.

## Contribution

The paper provides an updated review of HER2-targeted therapies, including drug types, clinical outcomes, and emerging treatment strategies for HER2-mutant NSCLC.

## Key findings

- Pyrotinib and trastuzumab deruxtecan are currently approved for HER2-mutant NSCLC but remain insufficient for clinical needs.
- New selective HER2 tyrosine kinase inhibitors are emerging as promising treatment options.
- Future treatment strategies are shifting toward combination therapies and precision selection methods.

## Abstract

人类表皮生长因子受体2（human epidermal growth factor receptor 2, HER2）突变在非小细胞肺癌（non-small cell lung cancer, NSCLC）中发挥着驱动基因的作用。HER2突变的晚期NSCLC患者对传统化疗和免疫治疗的疗效不佳，因此靶向HER2的治疗正在进行广泛的研究。本综述分析了HER2突变在NSCLC中的生物学特性、靶向治疗药物-包括大分子单抗、酪氨酸激酶抑制剂（tyrosine kinase inhibitors, TKIs）和抗体偶联药物的临床研究概况以及耐药研究方向。吡咯替尼和德曲妥珠单抗目前获批用于治疗标准治疗失败后的HER2突变晚期NSCLC患者，但远不能满足临床需求，新型选择性HER2 TKIs逐渐崭露头角。未来的探索趋势正在从单一的药物逐渐转向联合策略，并且探索更为精准的选择策略以及耐药机制研究。这些研究将为HER2突变晚期NSCLC的临床治疗策略提供理论依据，推动个体化治疗的发展。

HER2: human epidermal growth factor receptor 2; TKIs: tyrosine kinase inhibitors; TKD: tyrosine kinase domain; EMT: epithelial mesenchymal transformation; MAPK: mitogen-activated protein kinase; PI3K: phosphatidylinositol-3-kinase; P: phosphorylation.

Summary of targeted HER2 studies in HER2-mutant NSCLC

The data of the Destiny Lung02 study 5.4 mg/kg cohort was used for DS-8201, and monotherapy data were used for TKIs and ADC drugs. If multiple studies were combined, the calculation was made. The figures in the table represent the incidence of adverse reactions. mAb: monoclonal antibody.