Abstract
22033 Background: This study was conducted to assess the prognostic role of EGFR in metastatic gastric cancer (MGC), with a view towards the future introduction of anti-EGFR therapy for MGC. Methods: Tumor samples from pts who received first-line 5- fluorouracil, leucovorin and platinum for MGC within a phase III trial of the AIO were prospectively analyzed. The expression of EGFR was assessed by immunohistochemistry (IHC) and by real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Moreover, pAKT, pMAPK, HER2/neu, Ki-67, T-cells and VEGF-A were evaluated (by qRT-PCR and/or immunohistochemistry). Results: 288 samples from 168 out of 220 patients (pts) enrolled were analysed. EGFR was expressed in 47% of pts (1+, 24%; 2+, 39%; 3+, 37%). The expression was highest in intestinal type histology (48%) and surgically resected tissues (50%) and lowest in diffuse type histology (29%) and biopsy tissues (34%). There was no difference in EGFR expression between primary tumors and metastases (40%, each). HER2/neu over-expression (3+) was detected in 20.7% of pts. EGFR expression (any grade) correlated with prolonged median overall survival (10.8 months in EGFR+ and 8.2 months in EGFR- pts; log rank p=.026), but not with Response rate (RR) or progression-free survival. This correlation was maintained in the multivariate analysis (p=.028) and was independent from age, sex, ECOG, type of histology, treatment, liver and peritoneal involvement. Interestingly, within the group of EGFR+ tumors, the intensity of EGFR expression correlated inversely with response to chemotherapy and survival (RR: 53% v 32% v 19% in EGFR 1+ v 2+ v 3+ tumors, respectively; 2-sided p=.032). EGFR protein expression did not correlate with EGFR mRNA. Further correlative results (e.g. VEGF/pMAPK) will be presented. Conclusions: The pattern of the prognostic impact of EGFR in MGC was complex. EGFR expression (any grade) was a positive prognostic factor. However, once EGFR is expressed, over-expression represented a negative predictive factor. Author Disclosure Employment or Leadership Consultant or Advisory Role Stock Ownership Honoraria Research Expert Testimony Other Remuneration Siemens Medical Solutions
Published Version
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