Survival benefit of HER2-targeted or androgen deprivation therapy in salivary duct carcinoma

  • Daisuke Kawakita
    Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
  • Toshitaka Nagao
    Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Hideaki Takahashi
    Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan
  • Satoshi Kano
    Department of Otolaryngology – Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan
  • Yoshitaka Honma
    Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan
  • Hideaki Hirai
    Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Natsuki Saigusa
    Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Kohei Akazawa
    Department of Medical Informatics, Niigata University Medical and Dental Hospital, Chuo-ku, Niigata, Japan
  • Kaori Tani
    Department of Medical Informatics, Niigata University Medical and Dental Hospital, Chuo-ku, Niigata, Japan
  • Hiroya Ojiri
    Department of Radiology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan
  • Kiyoaki Tsukahara
    Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Hiroyuki Ozawa
    Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Kenji Okami
    Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Tokai University, Isehara, Japan
  • Takahito Kondo
    Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan
  • Takafumi Togashi
    Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan
  • Chihiro Fushimi
    Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Minato-ku, Tokyo, Japan
  • Tomotaka Shimura
    Department of Otolaryngology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan
  • Akira Shimizu
    Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Isaku Okamoto
    Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Takuro Okada
    Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Yorihisa Imanishi
    Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Yoshihiro Watanabe
    Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Kuninori Otsuka
    Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan
  • Akihiro Sakai
    Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Tokai University, Isehara, Japan
  • Koji Ebisumoto
    Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Tokai University, Isehara, Japan
  • Yuichiro Sato
    Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan
  • Keisuke Yamazaki
    Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan
  • Yushi Ueki
    Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan
  • Toyoyuki Hanazawa
    Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan
  • Yuki Saito
    Department of Otolaryngology – Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan
  • Mizuo Ando
    Department of Otorhinolaryngology/Head & Neck Surgery, Okayama University Graduate School of Medicine, Kita-ku, Okayama, Japan
  • Takashi Matsuki
    Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University School of Medicine, Minami-ku, Sagamihara, Japan
  • Masato Nakaguro
    Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan
  • Yukiko Sato
    Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan
  • Makoto Urano
    Department of Diagnostic Pathology, Bantane Hospital, Fujita Health University, School of Medicine, Nakagawa-ku, Nagoya, Japan
  • Yoshitaka Utsumi
    Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan
  • Shinji Kohsaka
    Division of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan
  • Takashi Saotome
    Division of Medical Oncology, Matsudo City Hospital, Matsudo, Japan
  • Yuichiro Tada
    Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, 1-4-3 Mita, Minato-ku, Tokyo 108-8329, Japan

抄録

<jats:sec><jats:title>Background:</jats:title><jats:p> The efficacy and safety of human epidermal growth factor receptor 2 (HER2)-targeted therapy and androgen deprivation therapy (ADT) for locally advanced or recurrent or metastatic (LA/RM) salivary duct carcinoma (SDC) have been reported in prospective studies. However, the survival benefit of these therapies to conventional therapy remains controversial, and whether HER2-targeted therapy or ADT should be chosen in HER2- and androgen receptor (AR)-positive SDC patients remains unknown. </jats:p></jats:sec><jats:sec><jats:title>Methods:</jats:title><jats:p> Overall, 323 LA/RM SDC patients treated at seven institutions between August 1992 and June 2020 were retrospectively enrolled. The primary aim was to analyze the effect of HER2-targeted therapy and ADT on overall survival from the diagnosis of LA/RM disease to death from any cause (OS1). The secondary indicators included the overall response rate (ORR), clinical benefit rate (CBR), overall survival from therapy initiation for LA/RM disease (OS2), progression-free survival (PFS), time to second progression (PFS2), duration of response (DoR), and duration of clinical benefit (DoCB) of HER2-targeted therapy or ADT as first-line therapy for HER2-positive/AR-positive SDC. </jats:p></jats:sec><jats:sec><jats:title>Results:</jats:title><jats:p> Patients treated with HER2-targeted therapy or ADT had longer OS1 than those treated without these therapies (Median OS1: historical control, 21.6 months; HER2-targeted therapy, 50.6 months; ADT, 32.8 months; HER2-targeted therapy followed by ADT, 42.4 months; and ADT followed by HER2-targeted therapy, 45.2 months, p < 0.001). Among HER2-positive/AR-positive SDC patients, although HER2-targeted therapy had better ORR, CBR, and PFS than those of ADT as first-line therapy, we found no significant differences between HER2-targeted therapy and ADT regarding OS2, PFS2, DoR, and DoCB. </jats:p></jats:sec><jats:sec><jats:title>Conclusion:</jats:title><jats:p> Patients treated with HER2-targeted therapy and ADT showed longer survival in LA/RM SDC. HER2-targeted therapy can be recommended prior to ADT for HER2-positive/AR-positive SDC. It is warranted to establish a biomarker that could predict the efficacy of clinical benefit or better response in ADT. </jats:p></jats:sec>

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