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)

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 Ishioka^1,2,11

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.

Keywords —— 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