作者
Kiichiro Ninomiya,Tae Hata,Hiroshige Yoshioka,Kadoaki Ohashi,Akihiro Bessho,Shinobu Hosokawa,Nobuhisa Ishikawa,Masahiro Yamasaki,Takuo Shibayama,Keisuke Aoe,Toshiyuki Kozuki,Shingo Harita,Yutaka Ueda,Toshi Murakami,Nobukazu Fujimoto,Hiroyuki Yanai,Shinichi Toyooka,Minoru Takata,Katsuyuki Hotta,Katsuyuki Kiura,Kenichi Gemba,Genyo Ikeda,Masayuki Yasugi,Etsuko Kurimoto,Kenji Nakano,Tomonori Moritaka,Koji Inoue,Seigo Miyoshi,Nobumasa Hamaguchi,Raquel Keiko de Luca Ito,Yusuke Sano,Ichiro Takata,Akihisa Mitani,Tsuyoshi Nishisaka,Hiroyasu Shoda,Akiko Nishida,Seika Tamamoto,Kazunori Fujitaka,Takeshi Masuda,Suzanne Miyamoto,Noboru Hattori,Keisuke Sugimoto,Satoshi Fujii,Yutaka Ueda,M. Sakugawa,Nobuaki Fukamatsu,Yoshitaka Ogata,Syuuji Bandoh,Nobuhiro Kanaji,Nagio Takigawa,Hiromichi Yamane,Nobuaki Ochi,Yoshihiro Honda,M. Oka,Makoto Kittaka,Tetsuya Kubota,Akihiro Yokoyama,Takuma Yokoyama,Eriko Sato,Yutaro Shiota,Naokatsu Horita,Takanori Kanematsu,Yoshikazu Awaya,A. Nakamasu,Isao Murakami,Shoichi Kuyama,Kenichiro Kudo,Takao Tamura,Takahiro Umeno,Daisuke Morichika,Kazuhisa Fujiwara,Kei Sato,Daijiro Harada,Naoyuki Nogami,Kazuya Nishii,Yasuko Fuchimoto,Tomoya Kishimoto,Hitomi Kawai,Keita Watanabe,Keizo Tokumo,Takashi Isobe,Yukari Tsubata,Masatoshi Inoue,Hirohisa Ichikawa,Yoshihiro Nishioka,Masaki Hashimoto,Hideko Goto,Takashi Sumikawa,Masahiro Kodani,Hisashi Suyama,Hirochika Makino,Naoki Kinosita,Eiichi Shimizu,Hideto Obata,Harumichi Ikegami,Kenichi Chikamori,Takeshi Maeda,Tomonori Kishino,Haruhito Kamei,Hiroshi Ueoka,Yamaoka Kunihiro,Taisuke Kobayashi,Kayo Ueda,Mikiko Hayashi,Mako Kamiya,Junichi Murakami,Akiko Satô,Eiki Ichihara,Toshio Kubo,Takashi Ninomiya,Taizo Hirata,Daisuke Minami,Yuka Kato,Hisao Higo,Go Makimoto,Yasunori Toyota,Naohiro Oda,Misuzu Nakanishi,Hiroe Kayatani,Satoru Senoo,Hirohisa Kano,Hiromu Watanabe,Takayuki Ando,Takamasa Nakasuka,Naofumi Hara,Junko Itano,Hiromi Nakashima,Masahiro Tabata
摘要
Background Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. Methods Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. Results Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor 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 patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. Conclusions This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations. Trial Registry UMIN Registration No. 000017003; URL: https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000019691 Human epidermal growth factor 2 (HER2) is a potential driver oncogene. Although HER2-targeted precision therapy has been tested in non-small cell lung cancer (NSCLC), the demographic characteristics of HER2-positive NSCLC have not been systematically defined. Patients with pathologically confirmed stage IIIB/IV or recurrent NSCLC, Eastern Cooperative Oncology Group performance status 0 to 2, were prospectively registered. HER2 immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) assays were performed to screen patients. HER2 mutations were identified by using direct gene sequencing. The aim of this study was to clarify the frequency, characteristics, and outcome of HER2-positive NSCLC. HER2 was defined as positive if the tumor harbored IHC3+, IHC2+/FISH+, or exon 20 insertion mutations. Of the 1,126 tumors screened, 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 epidermal growth factor receptor 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 patients had HER2-mutant tumors more frequently, whereas both IHC3+ and IHC2+/FISH+ tumors were detected more often in male subjects and smokers. Patients with an HER2-aberrant tumor had a significantly worse prognosis than those with epidermal growth factor receptor-positive and anaplastic lymphoma kinase-positive tumors, possibly due to the low proportion that received HER2-targeted therapies (n = 15 [26%]) and low response rates of 0% and 14% in patients with HER2-overexpressing and HER2-mutant tumors, respectively. This prospective large-scale cohort study is the first to show comprehensively the frequency and clinical demographic characteristics of those with HER2-positive advanced lung tumors in detail, providing critical historical data for future drug development against HER2-positive NSCLC. Future treatment strategies would be developed stratified according to the types of HER2 aberrations.