HER2 is a potential driver oncogene. HER2-targeted precision therapy has been tested in NSCLC. However, the demographics of HER2-positive NSCLC have not been defined systematically.
Pts with advanced NSCLC were registered. HER2-IHC and FISH assays were performed with commercial kits. HER2 mutations were identified by the direct sequencing. The aim of this study was to clarify the frequency, characteristics and outcome of HER2-positive NSCLC.
Of 1,126 tumors screened (Table A), 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 EGFR wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775_G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female pts had HER2 mutant tumors more frequently, while IHC/FISH+ tumors were detected more often in males (Table B). HER2-positive tumors had similar survival outcome to triple negative tumors, but significantly worse prognoses than EGFR-mutant and ALK-positive tumors (p
This is the first prospective study showing a small fraction of NSCLC possessed HER2 aberrations. HER2-positive tumors had relatively poor prognosis. NSCLCs with HER2 IHC3+ and mutation seemed to be distinct subsets.
Clinical trial identification
UMIN registration number 000017003
Legal entity responsible for the study
Japan Agency for Medical Research and Development
H. Yoshioka: Honoraria: Eli Lilly, Chugai Pharma., Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, AstraZeneca, Bristol-Myers Squibb, Ono Pharmaceutical, Takeda Pharma. T. Shibayama: Honoraria: Meiji Seika Pharma Co., Ltd. Astra Zeneca K.K. Boehringer Ingelheim Pharmaceuticals, Inc. Eli Lilly Japan K.K. K. Aoe: Eli Lilly, Astrazeneca, BMS, Ono Pharmaceutical Co., Ltd. T. Kozuki: Honoraria: Chugai Pharma., AstraZeneca, Eli lilly Japan, Pfizer, Ono Pharm., Bristol-Myers Squibb, Kyowa-Hakko Kirin, Boehringer Ingelheim. N. Fujimoto: Honoraria: Kissei Co. Ltd. S. Kuyama: Honoraria: Chugai Pharma., AstraZeneca, Pfizer, Ono Pharm., Boehringer Ingelheim, Meiji Seika Pharma. H. Yanai: Honoraria: Bayer Yakuhin, Ltd, Janssen Pharmaceutical K.K., Kyowa Hakko Kirin Co., Ltd., Becton, Dickinson and Company, Fujiyakuhin Co., Ltd. K. Kiura: Honoraria: Chugai Pharmaceutical Co., Ltd. Pfizer Japan Inc. Novartis Pharma K.K. Taiho Pharmceutical Co., Ltd. Eli Lilly Japan K.K. All other authors have declared no conflicts of interest.