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DOI: 10.1200/JCO.19.03077 Journal of Clinical Oncology - published online before print March 24, 2020
PMID: 32208960
Randomized, Phase II Study of Trastuzumab Beyond Progression in Patients With HER2-Positive Advanced Gastric or Gastroesophageal Junction Cancer: WJOG7112G (T-ACT Study)
2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
3Department of Hematology/Oncology, Saga University Hospital, Saga, Japan
4Department of Surgery, Kaizuka City Hospital, Osaka, Japan
5Department of Gastroenterology and Hematology, Faculty of Medicine, University of Toyama, Toyama, Japan
6Department of Clinical Oncology, St Marianna University School of Medicine, Kawasaki, Japan
7Department of Clinical Oncology, Kagawa University Faculty of Medicine, Kita-gun, Japan
8Division of Gastroenterology, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan
9Department of Clinical Oncology, Kawasaki Medical School, Okayama, Japan
10Division of Clinical Oncology, Hiroshima Prefectural Hospital, Hiroshima, Japan
11Department of Medical Oncology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
12Department of GI Oncology, Shizuoka Cancer Center, Shizuoka, Japan
13Department of Oncology, Izumi City General Hospital, Osaka, Japan
14Department of Surgery, National Hospital Organization Osaka National Hospital, Osaka, Japan
15Department of Gastroenterology, National Health Organization, Mito Medical Center, Ibaraki, Japan
16Department of Biostatistics, Yokohama City University, Yokohama, Japan
17Clinical Trial Coordination Unit and Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Shizuoka, Japan
18Division of Medical Oncology and Hematology, Oita University Faculty of Medicine, Oita, Japan
19Department of Gastrointestinal and Medical Oncology, National Hospital Organization Kyushu Cancer Center, Fukuoka, Japan
20Division of Gastrointestinal Medical Oncology, National Cancer Center Hospital, Tokyo, Japan
21Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan
This study evaluated the continuous use of trastuzumab beyond progression (TBP) in human epidermal growth factor receptor 2 (HER2)-positive advanced gastric or gastroesophageal junction (G/GEJ) cancer.
Patients with HER2-positive advanced G/GEJ cancer refractory to first-line chemotherapy with trastuzumab in combination with fluoropyrimidine and platinum were eligible. Patients were randomly assigned to the paclitaxel (80 mg/m2, days 1, 8, and 15, every 4 weeks) or paclitaxel with trastuzumab (PT; initially 8 mg/kg followed by 6 mg/kg, every 3 weeks) arms. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), response rate, and safety. Biomarkers such as HER2 expression status in tumor tissue after first-line treatment, HER2 amplification evaluated in serum cell-free DNA, and soluble HER2 levels were analyzed.
Overall, 91 patients were allocated to the paclitaxel (n = 46) and PT (n = 45) arms. The median PFS in the paclitaxel and PT arms was 3.2 and 3.7 months, respectively (hazard ratio [HR], 0.91; 80% CI, 0.67 to 1.22; P = .33), and the median OS in both arms was 10 months (HR, 1.2; 95% CI, 0.75 to 2.0; P = .20). The overall response rates in the paclitaxel and PT arms were 32% and 33%, respectively (P = 1.00), and safety was comparable between the 2 arms. On exploratory analyses, HER2 positivity of tumor tissues was lost after first-line chemotherapy in 11 (69%) of 16 patients whose tumor tissues were available, and circulating HER2 DNA amplification was detected in 41 (60%) of 68 patients. However, no biomarkers associated with efficacy of TBP were found.
Presented at the American Society of Clinical Oncology 2018 Annual meeting, Chicago, IL, June 1-5, 2018.
Supported in part by Cancer Clinical Trial Research Grant Program of Japan Society of Clinical Oncology.