Cancer

Internal medicine

Oncology

Lung cancer

Medicine

Cancer research

Epidermal growth factor receptor

Osimertinib

Clinical trial

Erlotinib

Clinical Cancer Research

Purpose: HER2 (or ERBB2) aberrations, including both amplification and mutations, have been classified as oncogenic drivers that contribute to 2% to 6% of lung adenocarcinomas. HER2 amplification is also an important mechanism for acquired resistance to EGFR tyrosine kinase inhibitors (TKI). However, due to limited preclinical studies and clinical trials, currently there is still no available standard of care for lung cancer patients with HER2 aberrations. To fulfill the clinical need for targeting HER2 in patients with non–small cell lung cancer (NSCLC), we performed a comprehensive preclinical study to evaluate the efficacy of a third-generation TKI, osimertinib (AZD9291). Experimental Design: Three genetically modified mouse models (GEMM) mimicking individual HER2 alterations in NSCLC were generated, and osimertinib was tested for its efficacy against these HER2 aberrations in vivo. Results: Osimertinib treatment showed robust efficacy in HER2wt overexpression and EGFR del19/HER2 models, but not in HER2 ex...

Targeting <i>HER2</i> Aberrations in Non–Small Cell Lung Cancer with Osimertinib

Targeting HER2 Aberrations in Non–Small Cell Lung Cancer with Osimertinib