Interaction between intratumoral ERCC1 expression and adjuvant treatment with S-1 on the survival of patients enrolled in the ACTS-GC study.

Abstract

53 Background: Excision repair cross-complementing group 1 (ERCC1) is thought to be involved in resistance to platinum-based therapy. Recently, expression of this gene was shown to be associated with the outcome in patients with gastric cancer. Biomarker analysis was conducted to evaluate the influence of this gene expression on the outcomes of patients enrolled in the ACTS-GC study, a randomized phase III trial, which demonstrated the efficacy of adjuvant treatment with S-1 after D2 dissection for stage II and III gastric cancer (Sakuramoto et al., NEJM 2007). Methods: Formalin-fixed paraffin-embedded specimens were available for 829 of a total of 1,059 (78.3%) patients. ERCC1 expression was measured by RT-PCR in the macrodissected tumor specimens and normalized to β-actin expression as the reference gene. The expression of ERCC1 was categorized into low and high values at the median. Results: The ERCC1 expression level was quantifiable in 97% of the 829 specimens and the distribution was balanced across the arms. In the S-1 group, overall survival (OS) tended to be longer in the high ERCC1 expression group than in the low ERCC1 expression group (HR, 0.698; 95% CI, 0.469-1.040; p= 0.076). On the contrary, in the surgery group, the OS was shorter in the high ERCC1 expression group than in the low ERCC1 expression group (HR, 1.216; 95% CI, 0.881-1.679; p= 0.232), although the difference was not statistically significant. The HR for OS of S-1 to surgery alone was smaller in the high-ERCC1 (HR, 0.465; 95% CI, 0.320-0.678) than in the low-ERCC1 group (HR, 0.805; 95% CI, 0.568-1.141). Significant interaction between the S-1 group and ERCC1 expression was observed (p= 0.033). Conclusions: This large biomarker study showed that intratumoral ERCC1 gene expression may be a predictive marker in gastric cancer patients receiving postoperative adjuvant chemotherapy with S-1.