Advanced Oesophagogastric Adenocarcinoma Research Articles

Biomarker analysis in oesophagogastric cancer: Results from the REAL3 and TransMAGIC trials

BackgroundREAL3 (Randomised ECF for Advanced or Locally advanced oesophagogastric cancer 3) was a phase II/III trial designed to evaluate the addition of panitumumab (P) to epirubicin, oxaliplatin and capecitabine (EOC) in untreated advanced oesophagogastric adenocarcinoma, or undifferentiated carcinoma. MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy) was a phase III study which demonstrated that peri-operative epirubicin, cisplatin and infused 5-fluourouracil (ECF) improved survival in early oesophagogastric adenocarcinoma. Patients and methodsAnalysis of response rate (RR; the primary end-point of phase II) and biomarkers in the first 200 patients randomised to EOC or modified dose (m) EOC+P in REAL3 was pre-planned to determine if molecular selection for the on-going study was indicated. KRAS, BRAF and PIK3CA mutations and PTEN expression were assessed in pre-treatment biopsies and results correlated with response to mEOC+P. Association between these biomarkers and overall survival (OS) was assessed in MAGIC patients to determine any prognostic effect. ResultsRR was 52% to mEOC+P, 48% to EOC. Results from 175 assessable biopsies: mutations in KRAS (5.7%), BRAF (0%), PIK3CA (2.5%) and loss of PTEN expression (15.0%). None of the biomarkers evaluated predicted resistance to mEOC+P. In MAGIC, mutations in KRAS, BRAF and PIK3CA and loss of PTEN (phosphatase and tensin homolog) were found in 6.3%, 1.0%, 5.0% and 10.9%, respectively, and were not associated with survival. ConclusionsThe RR of 52% in REAL3 with mEOC+P met pre-defined criteria to continue accrual to phase III. The frequency of the mutations was too low to exclude any prognostic or predictive effect.

Trastuzumab: a novel standard option for patients with HER-2-positive advanced gastric or gastro-oesophageal junction cancer

The human epidermal receptor-2 (HER-2) is amplified in up to 25% of patients with gastroesophageal adenocarcinomas. Although the presence of this amplification does not appear to confer a poor prognosis, it provides a valuable novel therapeutic target for this group of patients. Trastuzumab is a fully humanized monoclonal antibody directed at HER-2 which binds the external domain of the receptor and exerts its action via a combination of antibody-dependent cytotoxicity, reduced shedding of the extracellular domain, inhibition of dimerization and possibly receptor downregulation. The ToGA trial was an international multicentre randomized phase III study which evaluated the addition of trastuzumab to a cisplatin plus fluoropyrimidine chemotherapy doublet in 594 patients with HER-2-positive advanced gastric or oesophagogastric junction adenocarcinoma. The combination of the antibody with chemotherapy significantly improved response rate, median progression-free survival and median overall survival without additional toxicity or adversely affecting quality of life. Accordingly, trastuzumab plus chemotherapy is now a standard first-line treatment option for patients with advanced HER-2-positive gastroesophageal cancer. Unfortunately, many patients with HER-2-positive cancer exhibit primary resistance to trastuzumab and the remainder will acquire resistance to the antibody; therefore, urgent investigation into novel agents which may circumvent resistance mechanisms is warranted. Small molecule inhibitors of HER-2, which commonly also target other members of the HER family of receptors, such as EGFR and HER-3, are currently undergoing evaluation in gastroesophageal cancer as first-line alternatives to trastuzumab and second-line salvage treatments for trastuzumab-resistant disease. Extrapolating the successful use of trastuzumab in the advanced disease setting, clinical trials are underway to assess the role of this antibody in the perioperative and adjuvant settings, where it is hoped that it will have a meaningful impact upon the currently poor survival rates.

"DHA-paclitaxel has modest activity as monotherapy in patients with previously untreated advanced oesophago-gastric adenocarcinoma",

"DHA-paclitaxel has modest activity as monotherapy in patients with previously untreated advanced oesophago-gastric adenocarcinoma",

Phase I study of the humanized epidermal growth factor receptor (EGFR) antibody EMD 72000 (matuzumab) in combination with ECX (epirubicin, cisplatin and capecitabine) as first line treatment for advanced oesophagogastric (OG) adenocarcinoma

4028 Background: ECF (epirubicin, cisplatin and 5FU) is widely used for the treatment of advanced OG cancer. ECX, where capecitabine is substituted for 5FU has demonstrated comparable toxicity and ...

Final results of a phase 1 and PK study of capecitabine (XEL) in combination with epirubicin (E) and cisplatin (C) [ECC] in patients with advanced oesophagogastric (OG) adenocarcinoma

Final results of a phase 1 and PK study of capecitabine (XEL) in combination with epirubicin (E) and cisplatin (C) [ECC] in patients with advanced oesophagogastric (OG) adenocarcinoma