HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium

BACKGROUND Human epidermal growth factor receptor 2 (HER2) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with HER2 mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC). METHODS Patients with advanced‐stage lung adenocarcinomas were enrolled to the LCMC. Tumor specimens were assessed for diagnosis and adequacy; multiplexed genotyping was performed in Clinical Laboratory Improvement Amendments (CLIA)‐certified laboratories to examine 10 oncogenic drivers. The LCMC database was queried for patients with HER2 mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with HER2 mutations who were treated with HER2‐directed therapies. RESULTS A total of 920 patients were tested for HER2 mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%‐4%). One patient had a concurrent mesenchymal‐epithelial transition factor (MET) amplification. The median age of the patients was 62 years, with a slight predominance of females over males (14 females vs 10 males). The majority of the patients were never‐smokers (71%) and presented with advanced disease at the time of diagnosis. The median survival for patients who received HER2‐targeted therapies (12 patients) was 2.1 years compared with 1.4 years for those who did not (12 patients) (P = .48). Patients with HER2 mutations were found to have inferior survival compared with the rest of the LCMC cohort with other mutations: the median survival was 3.5 years in the LCMC population receiving targeted therapy and 2.4 years for patients not receiving targeted therapy. CONCLUSIONS HER2 mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2‐directed therapies should be investigated in this subgroup of patients. Cancer 2017;123:4099–4105. © 2017 American Cancer Society. In the current study, human epidermal growth factor receptor 2 (HER2) mutations are reported in 3% of patients with lung adenocarcinoma in the Lung Cancer Mutation Consortium. The survival of this subgroup of patients appears to be similar regardless of whether they received HER2‐targeted therapy, but further investigation of HER2‐targeted therapies may help to improve outcomes.