A Prospective Cohort Study to Define the Clinical Features and Outcome of Lung Cancers Harboring HER2 Aberration in Japan (HER2-CS STUDY)

Kiichiro Ninomiya, Tae Hata, Hiroshige Yoshioka, Kadoaki Ohashi, Akihiro Bessho, Shinobu Hosokawa, Nobuhisa Ishikawa, Masahiro Yamasaki, T. Shibayama, Keisuke Aoe, Toshiyuki Kozuki, Shingo Harita, Yutaka Ueda, T. Murakami, Nobukazu Fujimoto, Hiroyuki Yanai, Shinichi Toyooka, Minoru Takata, Katsuyuki Hotta, Katsuyuki KiuraK. Gemba, G. Ikeda, M. Yasugi, E. Kurimoto, K. Nakano, T. Moritaka, K. Inoue, S. Miyoshi, N. Hamaguchi, R. Ito, Y. Sano, I. Takata, A. Mitani, T. Nishisaka, H. Shoda, A. Nishida, S. Tamamoto, K. Fujitaka, T. Masuda, S. Miyamoto, N. Hattori, K. Sugimoto, S. Fujii, Y. Ueda, M. Sakugawa, N. Fukamatsu, Y. Ogata, S. Bandoh, N. Kanaji, N. Takigawa, H. Yamane, N. Ochi, Y. Honda, M. Oka, M. Kittaka, T. Kubota, A. Yokoyama, T. Yokoyama, E. Sato, Y. Shiota, N. Horita, T. Kanematsu, Y. Awaya, A. Nakamasu, I. Murakami, S. Kuyama, K. Kudo, T. Tamura, T. Umeno, D. Morichika, K. Fujiwara, K. Sato, D. Harada, N. Nogami, K. Nishii, Y. Fuchimoto, T. Kishimoto, H. Kawai, K. Watanabe, K. Tokumo, T. Isobe, Y. Tsubata, M. Inoue, H. Ichikawa, Y. Nishioka, M. Hanibuchi, H. Goto, T. Sumikawa, M. Kodani, H. Suyama, H. Makino, N. Kinosita, E. Shimizu, H. Obata, H. Ikegami, K. Chikamori, T. Maeda, T. Kishino, H. Kamei, H. Ueoka, Y. Kunihiro, T. Kobayashi, K. Ueda, M. Hayashi, M. Kamiya, J. Murakami, A. Sato, E. Ichihara, T. Kubo, T. Ninomiya, T. Hirata, D. Minami, Y. Kato, H. Higo, G. Makimoto, Y. Toyota, N. Oda, M. Nakanishi, H. Kayatani, S. Senoo, H. Kano, H. Watanabe, T. Ando, T. Nakasuka, N. Hara, J. Itano, H. Nakashima, M. Tabata

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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

Original languageEnglish
Pages (from-to)357-366
Number of pages10
JournalChest
Volume156
Issue number2
DOIs
Publication statusPublished - Aug 2019

Keywords

  • fluorescence in situ hybridization
  • human epidermal growth factor 2
  • immunohistochemistry
  • mutation
  • non-small cell lung cancer

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Ninomiya, K., Hata, T., Yoshioka, H., Ohashi, K., Bessho, A., Hosokawa, S., Ishikawa, N., Yamasaki, M., Shibayama, T., Aoe, K., Kozuki, T., Harita, S., Ueda, Y., Murakami, T., Fujimoto, N., Yanai, H., Toyooka, S., Takata, M., Hotta, K., ... Tabata, M. (2019). A Prospective Cohort Study to Define the Clinical Features and Outcome of Lung Cancers Harboring HER2 Aberration in Japan (HER2-CS STUDY). Chest, 156(2), 357-366. https://doi.org/10.1016/j.chest.2019.01.011