Impact of human epidermal growth factor receptor (EGFR) and ERBB2 (HER2) expressions on survival in patients with stage II/III gastric cancer, enrolled in the ACTS-GC study.

Abstract

4013 Background: EGFR and HER2 positivity is thought to be a negative prognostic factor in gastric cancer (GC). Biomarker analysis has been conducted to evaluate the influence of EGFR and HER2 expressions on the outcomes of patients (pts) enrolled in the ACTS-GC study, a randomized phase III trial, which demonstrated that adjuvant treatment with S-1 after D2 dissection for locally advanced GC was more effective as compared with surgery alone in East Asian pts (Sakuramoto et al., NEJM 2007) Methods: Formalin-fixed paraffin-embedded (FFPE) tissue specimens were examined retrospectively for EGFR and HER2 by immunohistochemistry (IHC) using Ventana antibody. The scores for EGFR and HER2 expression were centrally assessed in a blinded fashion. The expression of each of the genes was also measured by RT-PCR in macrodissected tumor specimens. Results: FFPE specimens were available from 829 of the total of 1,059 (78.3%) pts. As of the end of Dec. 2010, IHC for EGFR and HER2 had been performed for 489 and 670 pts, respectively, while the mRNA of each had been measured for 754 pts. The IHC score distribution for EGFR (grade 0, 20.2%; 1+, 47.4%; 2+, 22.3%; 3+, 10.0%) and that for HER2 (grade 0, 51.3%; 1+, 26.0%; 2+, 12.4%; 3+, 10.3%) were balanced across the arms. For both genes, the IHC score was significantly correlated with the mRNA expression level (P<0.0001, Wilcoxon’s test). EGFR 3+ status was associated with worse outcomes in the surgery alone group (OS, p=0.0098; HR 2.13 [95% CI:1.13-3.68]; RFS, p=0.0297; HR 1.94 [95% CI:1.003-3.41]) and the S-1 group (OS, p=0.0655; HR 1.87 [95% CI:0.895-3.51]; RFS, p=0.0237; HR 2.08 [95% CI:1.03-3.84]) These trends still remained significant in multivariate models in the surgery alone group (p=0.0277; HR 2.07 [95% CI:1.09-3.62]). No interaction for OS or RFS was observed between S-1 and the EGFR 3+ status. The HER2 status was not associated with the OS/RFS in either the surgery alone group or the S-1 group. Conclusions: This large biomarker study showed that the EGFR 3+ status was associated with worse outcomes in GC pts treated by surgery alone. The final results including the remaining FFPE specimens will be reported at the meeting.