REAL3: A multicenter randomized phase II/III trial of epirubicin, oxaliplatin, and capecitabine (EOC) versus modified (m) EOC plus panitumumab (P) in advanced oesophagogastric (OG) cancer—Response rate (RR), toxicity, and molecular analysis from phase II.

Abstract

4131 Background: EOC is a standard treatment option for advanced OG cancer. Epidermal growth factor receptor (EGFR) overexpression is common in OG cancer and associated with poor prognosis. P is a fully-human IgG2 monoclonal antibody targeting EGFR. Prospective data on the frequency of KRAS mutations are lacking and impact on RR to chemotherapy + P in OG cancer is unknown. Due to early toxicity with EOC+P (mainly grade 3 diarrhoea), a dose-finding study recommended reduced doses of O (100mg/m2) and C (1,000mg/m2/day) in the investigational arm in combination with E 50mg/m2 and P 9mg/kg (mEOC+P) given every 3 weeks for the phase II /III study (Okines et al., J Clin Oncol 2010). Methods: Patients with histologically proven, untreated advanced OG adenocarcinoma or undifferentiated carcinoma with measurable disease and adequate end-organ function were randomised to receive up to 8 cycles of EOC or mEOC+P. RR was assessed after 4 and 8 cycles. Toxicity was assessed 3-weekly during treatment. Codon 12 and 13 KRAS mutations in the diagnostic biopsy were detected using the Therascreen KRAS mutation kit (DXS). Nineteen patients (10 mEOC+P, 9 EOC) treated in the dose finding study were excluded from this analysis. The primary endpoint of the phase II study is RR to mEOC+P. Results: Between April 09 and September 10, 200 patients were randomly allocated to EOX (n=100) or mEOC+P (n=100): Median age 62, M:F 161:39, locally advanced: metastatic 20:180, oesophageal:OGJ:gastric 83:57:60.Of the 160 patients analysed thus far, 8 (5%) had KRAS mutations in codon 12 (n=5) and codon 13 (n=3). Conclusions: Response rate, toxicity and updated molecular analysis including the frequency of KRAS, BRAF and PIK3CA mutations will be reported. 328 of the planned 730 patients have been recruited so far in this on-going study.