Tohoku J. Exp. Med., 2021 May, 254(1)

Phase II Study of the Reuse of Trastuzumab with Docetaxel beyond Progression after First-Line Treatment in Second-Line Treatment for Unresectable, Metastatic Gastric Cancer (T-CORE1203)

Masanobu Takahashi,1,2 Yasuhiro Sakamoto,3 Kazunori Otsuka,4 Mariko Kanbe,5 Hisatsugu Ohori,6 Yoshiaki Shindo,7 Hiroshi Honda,8 Ken Saijo,1,2 Kota Ouchi,3 Yasuko Murakawa,4 Hidekazu Takahashi,6 Sadayuki Kawai,3 Yuichi Tanaka,7 Takuhiro Yamaguchi,9 Hideki Shimodaira,1,2 Takashi Yoshioka10 and Chikashi Ishioka1,2,11

1Department of Medical Oncology, Tohoku University Hospital, Sendai, Miyagi, Japan
2Department of Clinical Oncology, Institute of Development, Aging and Cancer, Tohoku University, Sendai, Miyagi, Japan
3Department of Medical Oncology, Osaki Citizen Hospital, Osaki, Miyagi, Japan
4Department of Medical Oncology, Miyagi Cancer Center, Natori, Miyagi, Japan
5Department of Internal Medicine, Senseki Hospital, Higashimatsushima, Miyagi, Japan
6Department of Clinical Oncology, Japanese Red Cross Ishinomaki Hospital, Ishinomaki, Miyagi, Japan
7Department of Gastroenterological Surgery, Nakadori General Hospital, Akita, Akita, Japan.
8Department of Surgery, Sendai Open Hospital, Sendai, Miyagi, Japan
9Division of Biostatistics, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan
10Department of Clinical Oncology, Yamagata University School of Medicine, Yamagata, Yamagata, Japan
11Department of Clinical Oncology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan

Whether trastuzumab use beyond disease progression is beneficial in second-line treatment for patients with unresectable human epidermal growth factor receptor 2 (HER2)-positive gastric cancer remains to be elucidated. We conducted this phase II study to assess whether trastuzumab plus docetaxel was effective for patients with previously treated advanced HER2-positive gastric cancer. This trial was a single-arm, open-label, multicenter, phase II study, conducted by Tohoku Clinical Oncology Research and Education Society (T-CORE). Patients aged 20 years or older who had advanced HER2-positive gastric cancer and were refractory to trastuzumab, fluoropyrimidine, and cisplatin were enrolled. Patients were treated with 6 mg/kg trastuzumab and 60 mg/m2 docetaxel every 3 weeks. The primary endpoint was the overall response rate. The threshold overall response rate was estimated to be at 15%. Secondary endpoints were progression-free survival, 6-month survival rate, overall survival, and toxicities. A total of 27 patients were enrolled from 7 hospitals. The median age was 67 years. Partial response was seen in 3 patients among the 26 evaluated patients. The overall response rate was at 11.5% (90% confidence interval 1.2%-21.8%). The median progression-free survival was 3.2 months, the 6-month survival rate was 85%, and the median overall survival was 11.6 months. Febrile neutropenia was observed in 14.8%. The most frequently observed grade 3 non-hematologic toxicity was anorexia (14.8%). The primary endpoint was not achieved. The results support a current consensus that the continuation of trastuzumab in second-line therapy for gastric cancer is not a recommended option.

Key words —— docetaxel; gastric cancer; HER2; reuse beyond progression; trastuzumab

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Tohoku J. Exp. Med 2021, 254, 49-55.

Correspondence: Chikashi Ishioka, Department of Clinical Oncology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan.

e-mail: chikashi@tohoku.ac.jp