Nozomu Fuse1, Yasutoshi Kuboki2, Takeshi Kuwata3,4, Tomohiro Nishina5, Shigenori Kadowaki6, Eiji Shinozaki7, Nozomu Machida8, Satoshi Yuki9, Akira Ooki10, Shinya Kajiura11, Tetsuo Kimura12, Takeharu Yamanaka13,14, Kohei Shitara2, Akiko Kawano Nagatsuma4, Takayuki Yoshino2, Atsushi Ochiai4, Atsushi Ohtsu15. 1. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. nofuse@east.ncc.go.jp. 2. Department of Gastrointestinal Oncology, National Cancer Center Hospital East, 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. 3. Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan. 4. Research Center for Innovative Oncology, National Cancer Center Hospital East, Kashiwa, Japan. 5. Department of Gastrointestinal Medical Oncology, Shikoku Cancer Center, Matsuyama, Japan. 6. Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Japan. 7. Gastroenterological Internal Medicine, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan. 8. Division of Gastrointestinal Oncology, Shizuoka Cancer Center, Nagaizumi, Japan. 9. Department of Gastroenterology and Hepatology, Hokkaido University Hospital, Sapporo, Japan. 10. Department of Gastroenterology, Saitama Cancer Center Hospital, Ina, Japan. 11. The Third Department of Internal Medicine, University of Toyama, Toyama, Japan. 12. Department of Gastroenterology and Oncology, The University of Tokushima Graduate School, Tokushima, Japan. 13. Department of Biostatistics, National Cancer Center, Kashiwa, Japan. 14. Department of Biostatistics, Yokohama City University, Yokohama, Japan. 15. Exploratory Oncology Research and Clinical Trial Center, National Cancer Center, Kashiwa, Japan.
Abstract
BACKGROUND: This study was conducted to investigate whether human epidermal growth factor receptor 2 (HER2) status, epidermal growth factor receptor (EGFR) status, and c-MET status are independent prognostic factors for advanced gastric cancer patients who received standard chemotherapy. METHOD: Unresectable or recurrent gastric or gastroesophageal junction cancer patients with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. Formalin-fixed paraffin-embedded tumor samples were examined for HER2, EGFR, and c-MET status using immunohistochemistry (IHC). Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as an IHC score of 3+ or an IHC score of 2+/FISH positive for HER2, and an IHC score of 2+ or 3+ for both EGFR and c-MET. RESULTS: Of the 293 patients from nine institutions, 43 (15%) were HER2 positive, 79 (27%) were EGFR positive, and 120 (41%) were c-MET positive. Ten patients (3%) showed positive co-expression of HER2, EGFR, and c-MET. After a median follow-up time of 58.4 months with 280 deaths, there was no significant difference in overall survival (OS) in terms of HER2 and EGFR status. However, there was a significant difference in OS between c-MET-positive and c-MET-negative patients [median, 11.9 months vs 14.2 months; hazard ratio, 1.31 (95% confidence interval, 1.03-1.67); log-rank P = 0.024]. Multivariate analysis also showed that c-MET positivity was still a prognostic factor for OS [hazard ratio, 1.30 (95% confidence interval, 1.02-1.67); P = 0.037]. CONCLUSIONS: The study suggested that c-MET-positive status had poor prognostic value. These data could be used as the basis for future clinical trials for targeting agents for advanced gastric cancer patients.
BACKGROUND: This study was conducted to investigate whether human epidermal growth factor receptor 2 (HER2) status, epidermal growth factor receptor (EGFR) status, and c-MET status are independent prognostic factors for advanced gastric cancerpatients who received standard chemotherapy. METHOD: Unresectable or recurrent gastric or gastroesophageal junction cancerpatients with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. Formalin-fixed paraffin-embedded tumor samples were examined for HER2, EGFR, and c-MET status using immunohistochemistry (IHC). Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as an IHC score of 3+ or an IHC score of 2+/FISH positive for HER2, and an IHC score of 2+ or 3+ for both EGFR and c-MET. RESULTS: Of the 293 patients from nine institutions, 43 (15%) were HER2 positive, 79 (27%) were EGFR positive, and 120 (41%) were c-MET positive. Ten patients (3%) showed positive co-expression of HER2, EGFR, and c-MET. After a median follow-up time of 58.4 months with 280 deaths, there was no significant difference in overall survival (OS) in terms of HER2 and EGFR status. However, there was a significant difference in OS between c-MET-positive and c-MET-negative patients [median, 11.9 months vs 14.2 months; hazard ratio, 1.31 (95% confidence interval, 1.03-1.67); log-rank P = 0.024]. Multivariate analysis also showed that c-MET positivity was still a prognostic factor for OS [hazard ratio, 1.30 (95% confidence interval, 1.02-1.67); P = 0.037]. CONCLUSIONS: The study suggested that c-MET-positive status had poor prognostic value. These data could be used as the basis for future clinical trials for targeting agents for advanced gastric cancerpatients.
Authors: Y Yonemura; I Ninomiya; A Yamaguchi; S Fushida; H Kimura; S Ohoyama; I Miyazaki; Y Endou; M Tanaka; T Sasaki Journal: Cancer Res Date: 1991-02-01 Impact factor: 12.701
Authors: Conor A Bradley; Manuel Salto-Tellez; Pierre Laurent-Puig; Alberto Bardelli; Christian Rolfo; Josep Tabernero; Hajrah A Khawaja; Mark Lawler; Patrick G Johnston; Sandra Van Schaeybroeck Journal: Nat Rev Clin Oncol Date: 2017-04-04 Impact factor: 66.675