Media type: E-Article Title: HER2 mutations in lung adenocarcinomas: A report from the Lung Cancer Mutation Consortium Contributor: Pillai, Rathi N.; Behera, Madhusmita; Berry, Lynne D.; Rossi, Mike R.; Kris, Mark G.; Johnson, Bruce E.; Bunn, Paul A.; Ramalingam, Suresh S.; Khuri, Fadlo R. imprint: Wiley, 2017 Published in: Cancer Language: English DOI: 10.1002/cncr.30869 ISSN: 1097-0142; 0008-543X Origination: Footnote: Description: <jats:sec><jats:title>BACKGROUND</jats:title><jats:p>Human epidermal growth factor receptor 2 (<jats:italic>HER2</jats:italic>) mutations have been reported in lung adenocarcinomas. Herein, the authors describe the prevalence, clinical features, and outcomes associated with <jats:italic>HER2</jats:italic> mutations in 1007 patients in the Lung Cancer Mutation Consortium (LCMC).</jats:p></jats:sec><jats:sec><jats:title>METHODS</jats:title><jats:p>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 <jats:italic>HER2</jats:italic> mutations to access demographic data, treatment history, and vital status. An exploratory analysis was performed to evaluate the survival of patients with <jats:italic>HER2</jats:italic> mutations who were treated with HER2‐directed therapies.</jats:p></jats:sec><jats:sec><jats:title>RESULTS</jats:title><jats:p>A total of 920 patients were tested for <jats:italic>HER2</jats:italic> mutations; 24 patients (3%) harbored exon 20 insertion mutations (95% confidence interval, 2%‐4%). One patient had a concurrent mesenchymal‐epithelial transition factor (<jats:italic>MET</jats:italic>) 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) (<jats:italic>P</jats:italic> = .48). Patients with <jats:italic>HER2</jats:italic> 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.</jats:p></jats:sec><jats:sec><jats:title>CONCLUSIONS</jats:title><jats:p><jats:italic>HER2</jats:italic> mutations were detected in 3% of patients with lung adenocarcinoma in the LCMC. HER2‐directed therapies should be investigated in this subgroup of patients. <jats:bold><jats:italic>Cancer</jats:italic> 2017;123:4099–4105.</jats:bold> © <jats:italic>2017 American Cancer Society</jats:italic>.</jats:p></jats:sec> Access State: Open Access