• Julien Mazières, Solange Peters, Benoit Lepage, Alexis B Cortot, Fabrice Barlesi, Michéle Beau-Faller, Benjamin Besse, Hélène Blons, Audrey Mansuet-Lupo, Thierry Urban, Denis Moro-Sibilot, Eric Dansin, Christos Chouaid, Marie Wislez, Joachim Diebold, Enriqueta Felip, Isabelle Rouquette, Julie D Milia, and Oliver Gautschi.
• Centre Hospitalier Universitaire de Toulouse, Université de Toulouse III, Toulouse Cedex, France. mazieres.j@chu-toulouse.fr
• J. Clin. Oncol. 2013 Jun 1; 31 (16): 1997-2003.

PurposeHER2 mutations are identified in approximately 2%of non-small-cell lung cancers (NSCLC). There are few data available that describe the clinical course of patients with HER2-mutated NSCLC.Patients And MethodsWe retrospectively identified 65 NSCLC, diagnosed with a HER2 in-frame insertion in exon 20. We collected clinicopathologic characteristics, patients' outcomes, and treatments.ResultsHER2 mutation was identified in 65 (1.7%) of 3,800 patients tested and was almost an exclusive driver, except for one single case with a concomitant KRAS mutation. Our population presented with a median age of 60 years (range, 31 to 86 years), a high proportion of women (45 women v 20 men; 69%), and a high proportion of never-smokers (n= 34; 52.3%). All tumors were adenocarcinomas and 50% were stage IV at diagnosis. For these latter cases, 22 anti-human epidermal growth factor receptor 2 (HER2) treatments were administered after conventional chemotherapy in 16 patients. Subsequently, four patients experienced progressive disease, seven experienced disease stabilizations, and 11 experienced partial responses (overall response rate, 50%; disease control rate [DCR], 82%). Specifically, we observed a DCR of 93% for trastuzumab-based therapies (n = 15) and a DCR of 100% for afatinib (n = 3) but no response to other HER2-targeted drugs (n = 3). Progression-free survival for patients with HER2 therapies was 5.1 months. Median survival was of 89.6 and 22.9 months for early-stage and stage IV patients, respectively.ConclusionThis study, the largest to date dedicated to HER2-mutated NSCLC, reinforces the importance of screening for HER2 mutations in lung adenocarcinomas and suggests the potential efficacy of HER2-targeted drugs in this population.

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