Prognostic significance of ki67, p53, TS and EGFR in advanced gastric and gastroesophageal junction cancer patients treated with cetuximab plus FOLFIRI (FOLCETUX study)

Abstract

4604 Background: The aim of this study was to evaluate the correlation between pathologic biomarkers and objective response (OR), time to progression (TTP) and overall survival (OS) in advanced gastric or gastroesophageal junction (GEJ) cancer patients (pts) treated with cetuximab plus FOLFIRI. Methods: We analysed 32/38 pts with stomach or GEJ locally advanced/metastatic adenocarcinoma, EGFR+, enrolled in the Italian FOLCETUX study. The pts were treated as first line with cetuximab weekly at 400 mg/m2 iv loading dose, and then at 250 mg/m2 iv maintenance dose, plus FOLFIRI every 2 weeks, for a maximum of 24 weeks, then cetuximab alone was allowed in pts with CR/PR/SD. Expression of Ki67, p53, TS and EGFR was examined immunohistochemically in primary tumor and/or metastasis samples. Ki67, p53 and TS were categorized into a low and high value; EGFR was categorized into low, intermediate and high values. High cut-off was defined as: >50% Ki67; >20% p53; =9% cytoplasmatic and >30% nuclear TS; EGFR score (combining % neoplastic cell positive and intensity) was: low=0–2, intermediate=3–5, high=6–7. To avoid any discrepant evaluation the assessment was carried out centrally by just one pathologist. Results: The pt characteristics were: 22M/10F; median age 64.5 years (39–83); stomach 29(90.6%), GEJ 3(9.4%); intestinal histotype 21(65.6%), non-intestinal 11(34.4%); locally advanced disease 4(12.5%), metastatic disease 28(87.5%). The OR were: 15 CR+PR, 15 SD, 2 PD. No relationship was observed between Ki67, p53, TS and EGFR expression and OR (Chi-squared test/Fisher’s Exact Test). In the multivariate analysis adjusted for the impact of intestinal/non-intestinal histotype and locally advanced/metastatic disease, the low TS expression was associated with an improved TTP ( Table 1 ). Conclusions: This results suggest that TS, EGFR, p53 and Ki67 expressions are not significantly correlated with OR. Low TS expression is predictive of better TTP. [Table: see text] No significant financial relationships to disclose.