• Fei Xu, Guangjian Yang, Haiyan Xu, Lu Yang, Weini Qiu, and Yan Wang.
• Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
• Thorac Cancer. 2020 Mar 1; 11 (3): 679-685.

BackgroundHER2 mutation is found in 1%-2% of lung cancer patients. Studies comparing chemotherapy to HER2-TKIs are limited. This study aimed to investigate the molecular and clinical patterns of HER2 mutations in advanced non-small cell lung cancer (NSCLC), and compare the different outcomes between chemotherapy and HER2-TKIs.MethodsAdvanced or recurrent non-small cell lung cancer patients with de novo HER2 mutations (N = 75) were included in this study. Molecular information, clinical features, and treatment outcomes were retrospectively collected from a web-based patient registry and hospital chart review.ResultsBetween October 2012 and December 2018, 65 patients with in-frame insertion mutations, eight with point mutations and two with gene amplification were found. The most common subtypes of insertion mutations were A775_G776insYVMA, G776delinsVC, and V777_G778insGSP. HER2 mutated patients were mostly young-aged, females, never or light smokers, with adenocarcinoma. Chemotherapy achieved better outcomes than HER2-TKIs (median PFS: 5.5 vs. 3.7 months in the first-line setting and 4.2 vs. 2.0 months in the second-line setting, P = 0.001 and 0.031, respectively). In particular for the most common subtype, YVMA insertions, PFS was significantly longer in chemotherapy than HER2-TKIs both in the first-line (6.0 vs. 2.6 months, P = 0.008) and the second-line (4.2 vs. 2.6 months P < 0.001).ConclusionsHER2 mutated lung cancer patients were younger, mostly females, never or light smokers, with histologically diagnosed adenocarcinomas. Compared with afatinib, chemotherapy might bring more benefit to HER2 mutated advanced lung cancer patients, especially the most common type of HER2 exon 20 insertions, A775_G776insYVMA subtype.Key PointsChemotherapy achieved better outcomes than afatinib for Chinese HER2 mutated advanced NSCLC patients, especially for the most common subtype, YVMA insertions.© 2020 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.

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