Results of docetaxel plus oxaliplatin (DOCOX) ± cetuximab in patients with metastatic gastric and/or gastroesophageal junction adenocarcinoma: results of a randomised Phase 2 study

Eur J Cancer. 2013 Sep;49(13):2823-31. doi: 10.1016/j.ejca.2013.04.022. Epub 2013 Jun 5.

Abstract

Background: Patients with advanced adenocarcinoma of the gastroesophageal junction/stomach are treated by combination chemotherapy, with minimal improvements in survival. We evaluated adding cetuximab to combination chemotherapy in these patients.

Methods: The primary objective was progression-free survival. Secondary objectives were response rate, time to response, duration of response and safety. Treatment Arm 1: docetaxel+oxaliplatin (DOCOX)=docetaxel 60 mg/m(2) plus oxaliplatin 130 mg/m(2) on Day 1 of each 21-day cycle. Arm 2: docetaxel+oxaliplatin+cetuximab (DOCOX+C)=DOCOX with C 400mg/m(2) first dose then 250 mg/m(2) weekly. The protocol was amended to allow collection of tissue to correlate responses with KRAS status.

Findings: One hundred fifty patients were enrolled (75/arm). DOCOX/DOCOX+C: gastric 44%/41%, gastroesophageal junction 51%/55%, both 5%/4%. Response rate/arm: 26.5%/38.0%. Median progression-free survival: 4.7/5.1 months (95% confidence interval (CI) 3.0-5.6/4.3-5.9); 1 year survival: 39.1%/33.0%, median overall survival: 8.5/9.4 months; median duration of response: 7.3/5.6months. Grade 3-4 treatment-related adverse events (%) included neutropenia (50%/44%), febrile neutropenia (13%/19%), diarrhoea (12%/17%), fatigue (12%/17%) and leukopenia (7%/14%). Discontinuation was due to progressive disease 39/32 and adverse events 21/34. KRAS was collected on some patients 2 years into the study because of new American Society of Clinical Oncology (ASCO) findings.

Interpretation: Cetuximab added to DOCOX may improve response rate minimally; there appears to be no improvement in progression-free survival, overall survival or 1-year survival. Cetuximab added to DOCOX did not produce clinically significant outcomes. Toxicities were consistent with the study drugs' known safety profiles. KRAS mutation was infrequent; no conclusions can be drawn from KRAS response data. ClinicalTrial.gov Identifier: NCT00517829.

Keywords: Adenocarcinoma; Drug therapy; Gastroesophageal junction; KRAS.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / drug therapy*
  • Adenocarcinoma / genetics
  • Adenocarcinoma / mortality
  • Adenocarcinoma / secondary
  • Adult
  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Cetuximab
  • Disease-Free Survival
  • Docetaxel
  • Drug Administration Schedule
  • Esophageal Neoplasms / drug therapy*
  • Esophageal Neoplasms / genetics
  • Esophageal Neoplasms / mortality
  • Esophageal Neoplasms / pathology
  • Esophagogastric Junction / pathology*
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Mutation
  • Organoplatinum Compounds / administration & dosage
  • Oxaliplatin
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins p21(ras)
  • Stomach Neoplasms / drug therapy*
  • Stomach Neoplasms / genetics
  • Stomach Neoplasms / mortality
  • Stomach Neoplasms / pathology
  • Taxoids / administration & dosage
  • Time Factors
  • Treatment Outcome
  • United States
  • ras Proteins / genetics

Substances

  • Antibodies, Monoclonal, Humanized
  • KRAS protein, human
  • Organoplatinum Compounds
  • Proto-Oncogene Proteins
  • Taxoids
  • Oxaliplatin
  • Docetaxel
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins
  • Cetuximab

Supplementary concepts

  • Adenocarcinoma Of Esophagus

Associated data

  • ClinicalTrials.gov/NCT00517829