626P - Prognostic impact of HER2, EGFR, and c-MET status on overall survival of advanced gastric cancer patients treated with standard chemotherapy withou...

Date 29 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anticancer Agents
Gastric Cancer
Pathology/Molecular Biology
Translational Research
Basic Scientific Principles
Basic Principles in the Management and Treatment (of cancer)
Biological Therapy
Presenter Eiji Shinozaki
Citation Annals of Oncology (2014) 25 (suppl_4): iv210-iv253. 10.1093/annonc/mdu334
Authors E. Shinozaki1, N. Fuse2, Y. Kuboki2, T. Kuwata3, T. Nishina4, S. Kadowaki5, N. Machida6, S. Yuki7, A. Ooki8, S. Kajiura9, T. Kimura10, T. Yamanaka11, T. Sasaki6, K. Shitara2, A. Nagatsuma3, T. Yoshino12, A. Ochiai13, A. Ohtsu14
  • 1Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 135-8550 - Tokyo/JP
  • 2Department Of Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 3Research Center For Innovative Oncology, National Cancer Center Hospital East; Chiba, Japan, Kashiwa/JP
  • 4Department Of Internal Medicine, National Hospital Organization Shikoku Cancer Center, Matsuyama/JP
  • 5Department Of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya/JP
  • 6Division Of Gastrointestinal Oncology, Shizuoka Cancer Center, 411-8777 - Shizuoka/JP
  • 7Gastroenterology And Hepatology, Hokkaido University Hospital, 064-0804 - Sapporo/JP
  • 8Department Of Gastroenterology And Oncology, Saitama Cancer Center, Saitama/JP
  • 9The Third Departoment Of Internal Medicine, University of Toyama, Toyama/JP
  • 10Department Of Gastroenterology And Oncology, The University of Tokushima Graduate School, Tokushima/JP
  • 11Research Center For Innovative Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 12Gastrointestinal Oncology, National Cancer Center Hospital East, Kashiwa/JP
  • 13Research Center For Innovative Oncology, Pathology, National Cancer Center Hospital East, 277-8577 - Kashiwa/JP
  • 14Research Center For Innovative Oncology, National Cancer Center Hospital East, JP-277-8577 - Kashiwa/JP



Trastuzumab is the 1st molecular targeting drug that has been shown to confer overall survival benefit adding to chemotherapy in HER2-positive advanced gastric cancer (AGC). Although HER2, EGFR and c-MET have been extensively investigated, these prognostic impact on overall survival (OS) in AGC patients treated with standard chemotherapy without trastuzumab for first-line treatment remains controversial. This study was conducted to investigate the correlation of HER2, EGFR and c-Met status with prognosis, and clinicopathological features in AGC patients who received standard chemotherapy.


A total of 293 AGC patients from 9 institutes with histologically confirmed adenocarcinoma treated with S-1 plus cisplatin as first-line chemotherapy were eligible. HER2, EGFR, and c-MET were evaluated by immunohistochemistry (IHC) using formalin-fixed paraffin-embedded tumor samples. Additionally, gene amplification was examined using fluorescent in situ hybridization (FISH) for HER2. Positivity was defined as IHC 3+ or IHC 2 + /FISH+ for HER2 and IHC 2+ or 3+ for both EGFR and c-MET.


Among the 293 patients analyzed, 43 (15%) were HER2-positive, 79 (27%) were EGFR-positive and 120 (41%) were c-MET-positive. Only 10 (3%) patients showed positive co-expression for all three molecules. Median follow-up time was 58.4 months with 280 death events. There was no significant difference in 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 vs. 14.2 months; hazard ratio, 1.31 [95% confidence interval (CI), 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, 1.32 [95% CI, 1.02–1.69]; P = 0.033).


The present study suggested that c-MET-positive AGC patients had a poorer prognosis than c-Met-negative patients, and that HER2 and EGFR status had no prognostic value in terms of OS in AGC patients treated with conventional chemotherapy as a first-line treatment.


E. Shinozaki: Honoraria - Taiho Pharm., Chugai Pharm., Bristol-Myers Squibb, Merck Serono, Takeda Pharm., Yakult Honsha, Novartis, Mochida pharm., Otsuka pharm; N. Fuse: Honoraria - Chugai Pharma; Taiho Pharmaceutical Research Funding - Chugai Pharma; Taiho Pharmaceutical; Daiichi Sankyo; T. Nishina: Honoraria - Chugai Pharma; Taiho Pharmaceutical; S. Yuki: Honoraria - Taiho Pharmaceutical, Chugai Pharmaceutical, Bristol-Myers Squibb, Merck Serono, Takeda Pharmaceutical, Yakult Honsha; T. Yamanaka: Honoraria - Chugai Pharma; Taiho Pharmaceutical; T. Yoshino: Consultant or Advisory Role - None Honoraria - Takeda, Chugai and MerckSerono Research Funding - Daiichi Sankyo, Taiho, Bayer, Eli Lilly, Pfizer, Chugai, and Yakult; A. Ohtsu: Honoraria - Chugai Pharma; Roche; Taiho Pharmaceutical. All other authors have declared no conflicts of interest.