Clinical characteristics and prognostic factors of patients with non-small cell lung cancer having HER2 alterations

Human epidermal growth factor 2 (HER2) alterations are found in approximately 2%-5% of non-small cell lung cancer (NSCLC). This study aimed to evaluate the clinical characteristics of patients with NSCLC having HER2 alterations in China and the differences compared with Western counterparts and also perform a prognostic analysis.A total of 1300 patients diagnosed with NSCLC from January 2017 to December 2020 were included. Their clinical characteristics were retrospectively recorded. The gene expression profiles and clinical information of 20 patients having altered HER2 were downloaded from the Cancer Genome Atlas database and compared, and the prognostic factors affecting the Chinese population were analyzed. If tissues were sufficient, the overexpression was assessed by immunohistochemical staining.Among 39 (3.0%) patients with HER2 alterations, 31 patients (79.5%) had HER2 mutations. HER2 insertion mutation in exon 20 was the most common type (A775_G776 ins YVMA). Seven patients (17.9%) had amplification, and one had both. The HER2 kinase domain was most commonly mutated. A majority of patients in the study were young-aged with no smoking history; 66.7% had stage III/IV adenocarcinoma. Compared with Chinese patients, HER2 alterations in Western counterparts were mostly associated with old age, previous smoking, and stages I and II at diagnosis. The most common type of HER2 alteration was HER2 amplification; one patient had coexistence of HER2 gene amplification and fusion. The furin-like cysteine-rich region was most commonly mutated. The median overall survival (OS) of the Chinese patients was 41 months. The univariate analysis showed that age > 60 years, no surgical treatment, no liver or renal cysts on imaging, and maximum tumor diameter ≥ 4.25 cm were significantly associated with poor OS. The multivariate analysis showed that age, presence of surgery, and no hepatic or renal cysts were independent prognostic factors for OS. Chemotherapy achieved better outcomes, and HER2 mutations were not associated with HER2 amplification and overexpression.This study was novel in comprehensively investigating the clinical and molecular characteristics of patients in Chinese and Western populations, and in analyzing the factors affecting the prognosis of Chinese patients. It provided critical data for future therapies against HER2-altered NSCLC.