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

Daisuke Kawakita; Toshitaka Nagao; Hideaki Takahashi; Satoshi Kano; Yoshitaka Honma; Hideaki Hirai; Natsuki Saigusa; Kohei Akazawa; Kaori Tani; Hiroya Ojiri; Kiyoaki Tsukahara; Hiroyuki Ozawa; Kenji Okami; Takahito Kondo; Takafumi Togashi; Chihiro Fushimi; Tomotaka Shimura; Akira Shimizu; Isaku Okamoto; Takuro Okada; Yorihisa Imanishi; Yoshihiro Watanabe; Kuninori Otsuka; Akihiro Sakai; Koji Ebisumoto; Yuichiro Sato; Keisuke Yamazaki; Yushi Ueki; Toyoyuki Hanazawa; Yuki Saito; Mizuo Ando; Takashi Matsuki; Masato Nakaguro; Yukiko Sato; Makoto Urano; Yoshitaka Utsumi; Shinji Kohsaka; Takashi Saotome; Yuichiro Tada

doi:10.1177/17588359221119538

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

Ther Adv Med Oncol. 2022 Sep 6:14:17588359221119538. doi: 10.1177/17588359221119538. eCollection 2022.

Authors

Daisuke Kawakita¹, Toshitaka Nagao², Hideaki Takahashi³, Satoshi Kano⁴, Yoshitaka Honma⁵, Hideaki Hirai², Natsuki Saigusa², Kohei Akazawa⁶, Kaori Tani⁶, Hiroya Ojiri⁷, Kiyoaki Tsukahara⁸, Hiroyuki Ozawa⁹, Kenji Okami¹⁰, Takahito Kondo¹¹, Takafumi Togashi¹², Chihiro Fushimi¹³, Tomotaka Shimura¹⁴, Akira Shimizu⁸, Isaku Okamoto⁸, Takuro Okada⁸, Yorihisa Imanishi⁹, Yoshihiro Watanabe⁹, Kuninori Otsuka⁹, Akihiro Sakai¹⁰, Koji Ebisumoto¹⁰, Yuichiro Sato¹², Keisuke Yamazaki¹⁵, Yushi Ueki¹⁵, Toyoyuki Hanazawa¹⁶, Yuki Saito¹⁷, Mizuo Ando¹⁸, Takashi Matsuki¹⁹, Masato Nakaguro²⁰, Yukiko Sato²¹, Makoto Urano²², Yoshitaka Utsumi², Shinji Kohsaka²³, Takashi Saotome²⁴, Yuichiro Tada²⁵

Affiliations

¹ Department of Otorhinolaryngology, Head and Neck Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan.
² Department of Anatomic Pathology, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
³ Department of Otorhinolaryngology, Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.
⁴ Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Sapporo, Japan.
⁵ Department of Head and Neck, Esophageal Medical Oncology, National Cancer Center Hospital, Chuo-ku, Tokyo, Japan.
⁶ Department of Medical Informatics, Niigata University Medical and Dental Hospital, Chuo-ku, Niigata, Japan.
⁷ Department of Radiology, The Jikei University School of Medicine, Minato-ku, Tokyo, Japan.
⁸ Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University, Shinjuku-ku, Tokyo, Japan.
⁹ Department of Otorhinolaryngology, Head and Neck Surgery, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan.
¹⁰ Department of Otolaryngology, Head and Neck Surgery, School of Medicine, Tokai University, Isehara, Japan.
¹¹ Department of Otorhinolaryngology, Head and Neck Surgery, Tokyo Medical University Hachioji Medical Center, Hachioji, Japan.
¹² Department of Head and Neck Surgery, Niigata Cancer Center Hospital, Niigata, Japan.
¹³ Department of Head and Neck Oncology and Surgery, International University of Health and Welfare, Mita Hospital, Minato-ku, Tokyo, Japan.
¹⁴ Department of Otolaryngology, Showa University Fujigaoka Hospital, Aoba-ku, Yokohama, Japan.
¹⁵ Department of Otolaryngology Head and Neck Surgery, Niigata University Graduate School of Medical and Dental Sciences, Chuo-ku, Niigata, Japan.
¹⁶ Department of Otorhinolaryngology/Head & Neck Surgery, Chiba University Graduate School of Medicine, Chuo-ku, Chiba, Japan.
¹⁷ Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo, Japan.
¹⁸ Department of Otorhinolaryngology/Head & Neck Surgery, Okayama University Graduate School of Medicine, Kita-ku, Okayama, Japan.
¹⁹ Department of Otorhinolaryngology, Head and Neck Surgery, Kitasato University School of Medicine, Minami-ku, Sagamihara, Japan.
²⁰ Department of Pathology and Laboratory Medicine, Nagoya University Hospital, Nagoya, Japan.
²¹ Division of Pathology, Cancer Institute Hospital, Japanese Foundation for Cancer Research, Koto-ku, Tokyo, Japan.
²² Department of Diagnostic Pathology, Bantane Hospital, Fujita Health University, School of Medicine, Nakagawa-ku, Nagoya, Japan.
²³ Division of Cellular Signaling, National Cancer Center Research Institute, Chuo-ku, Tokyo, Japan.
²⁴ Division of Medical Oncology, Matsudo City Hospital, Matsudo, Japan.
²⁵ 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.

Abstract

Background: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: HER2; HER2-targeted therapy; androgen deprivation therapy; androgen receptor; salivary duct carcinoma.