Abstract CT137: Phase II study of trastuzumab and docetaxel therapy in patients with HER2-positive recurrent and/or metastatic salivary gland carcinoma
Authors: Kinoshita Ichiro , Kano Satoshi , Shimizu Yasushi , Kiyota Naomi , Tada Yuichiro , Ijichi Kei , Yamazaki Tmoko , Homma Akihiro , Ito Yoichi M. , Ono Kota , Kobayashi Keiko , Isoe Toshiyuki , Hatanaka Yutaka , Tsuda Hitoshi , Morinaga Shojiroh , Matsuno Yoshihiro , Dosaka-Akita Hirotoshi 
Published: August 2019

Abstract
Objectives: Salivary gland cancer is a rare cancer that has no effective drug therapy available. It comprises salivary duct carcinoma (SDC) as a major histology, which resembles high-grade breast ductal carcinoma and often overexpresses HER2. The purpose of this study is to evaluate the efficacy and safety of trastuzumab and docetaxel therapy in patients (pts) with HER2-positive salivary gland carcinoma.
Methods: We conducted a multicenter, single-arm Phase II study of trastuzumab and docetaxel for pts with HER2-positive recurrent and/or metastatic salivary gland carcinoma pursuant to the J-GCP. HER2 positivity was defined as immunohistochemistry (IHC) 3+ or IHC 2+/dual color in situ hybridization (DISH) +. Eligible pts were treated with trastuzumab 6 mg/kg (loading dose 8 mg/kg) and docetaxel 70 mg/m2 every 3 weeks up to 8 cycles. The primary endpoint was overall response rate (ORR) using RECIST v1.1 assessed by the blinded independent review committee (BIRC). Secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. This study required 16 pts, with ORR of 25% considered non-promising and 70% promising (two-sided alpha = 0.05; beta = 0.1) and with 2 withdrawal pts.
Results: Sixteen pts were recruited in this trial. The median age was 59 (range 26-72), 3 pts were female, and all pts had performance status 0-1. All pts had carcinomas histologically compatible with SDCs by central pathology review of samples used for HER2 evaluation, 14 of which were readily confirmed as SDCs. All pts had HER2 IHC 3+ tumors. Two pts were previously untreated and had metastatic disease. The remaining 14 pts had recurrence after surgery that was followed by adjuvant chemoradiotherapy in 5 pts and by adjuvant radiotherapy in 6 pts. No pts were previously treated with chemotherapy alone. After excluding a pt without measurable lesions evaluated by BIRC, ORR by BIRC was 60% (9/15; 95% CI, 32.3~83.7) with one complete response. Median PFS was 8.5 months (95% CI, 6.0~12.7). Median OS was not reached at a median follow-up of 17.9 months in survivors. Common grade 3/4 adverse events (&gt; 10%) were neutropenia (16 pts, 100%), leukopenia (15 pts, 93.8%), lymphopenia (3 pts, 18.8%), and febrile neutropenia (2 pts, 12.5%). Treatment-related death occurred in 1 pt (6.3%) due to hypoalbuminemia.
Conclusions: This study demonstrated a promising efficacy with predictable toxicities. Trastuzumab and docetaxel therapy may be an effective treatment option in pts with HER2-positive recurrent and/or metastatic salivary gland carcinoma.
Citation Format: Ichiro Kinoshita, Satoshi Kano, Yasushi Shimizu, Naomi Kiyota, Yuichiro Tada, Kei Ijichi, Tmoko Yamazaki, Akihiro Homma, Yoichi M. Ito, Kota Ono, Keiko Kobayashi, Toshiyuki Isoe, Yutaka Hatanaka, Hitoshi Tsuda, Shojiroh Morinaga, Yoshihiro Matsuno, Hirotoshi Dosaka-Akita. Phase II study of trastuzumab and docetaxel therapy in patients with HER2-positive recurrent and/or metastatic salivary gland carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT137.