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Bending the Curve Trial by Trial
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REAL-2

Capecitabine and oxaliplatin for advanced esophagogastric cancer

Phase 3N = 1,002

Population
Untreated advanced oesophagogastric cancer. The ISRCTN registry entry lists histologically verified adenocarcinoma, squamous cell or undifferentiated carcinoma of the oesophagus, oesophago-gastric junction or stomach; the abstract does not give the histology mix or HER2 status.
Design
Two-by-two randomised design: 1002 patients with untreated advanced oesophagogastric cancer were assigned to triplet therapy with epirubicin and cisplatin plus either fluorouracil (ECF) or capecitabine (ECX), or epirubicin and oxaliplatin plus either fluorouracil (EOF) or capecitabine (EOX). Primary endpoint: noninferiority in overall survival for the capecitabine-containing triplets versus fluorouracil, and for the oxaliplatin-containing triplets versus cisplatin (predefined margin 1.23 for the upper limit of the hazard-ratio confidence interval). Registered as ISRCTN51678883 (printed in the abstract; the registry entry titles it 'The REAL-2 Study' and labels it phase II/III). The phase 3 label here is the PubMed publication type (Clinical Trial, Phase III); the abstract does not state it.
Primary endpoint
OS
Arms
  • ECF (control): Epirubicin, cisplatin and fluorouracil
  • ECX (experimental): Epirubicin, cisplatin and capecitabine
  • EOF (experimental): Epirubicin, oxaliplatin and fluorouracil
  • EOX (experimental): Epirubicin, oxaliplatin and capecitabine
People
Cunningham D, Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom
OSHR 0.86 (95% CI 0.80–0.99)OSHR 0.92 (95% CI 0.8–1.1)Δ median OS0 monthsΔ 12-month OS+3.1 pointsOSHR 0.80 (95% CI 0.66–0.97)Δ median OS+1.3 months
Show the numbers
Results reported for REAL-2
EndpointAnalysisECX / EOF / EOXECFEffect
OSAll randomised patients in the capecitabine versus fluorouracil comparison (population not defined in the abstract)primaryCunningham 2008——HR 0.86 (95% CI 0.80–0.99)Noninferiority comparison: the upper limit of the confidence interval excluded the predefined margin of 1.23.
OSAll randomised patients in the oxaliplatin versus cisplatin comparison (population not defined in the abstract)primaryCunningham 2008——HR 0.92 (95% CI 0.8–1.1)Noninferiority comparison: the upper limit of the confidence interval excluded the predefined margin of 1.23.
OSAll randomised patients (population not defined in the abstract)primaryCunningham 2008median 9.9 months; 40.8% at 12 momedian 9.9 months; 37.7% at 12 mo—
OSAll randomised patients (population not defined in the abstract)exploratoryCunningham 2008median 11.2 monthsmedian 9.9 monthsHR 0.80 (95% CI 0.66–0.97)P=0.02Labelled a secondary analysis in the abstract; progression-free survival and response rates did not differ significantly among the regimens.
Results reported for REAL-2
EndpointAnalysisECX / EOF / EOXECFEffect
OSAll randomised patients in the capecitabine versus fluorouracil comparison (population not defined in the abstract)primaryCunningham 2008——HR 0.86 (95% CI 0.80–0.99)Noninferiority comparison: the upper limit of the confidence interval excluded the predefined margin of 1.23.
OSAll randomised patients in the oxaliplatin versus cisplatin comparison (population not defined in the abstract)primaryCunningham 2008——HR 0.92 (95% CI 0.8–1.1)Noninferiority comparison: the upper limit of the confidence interval excluded the predefined margin of 1.23.
OSAll randomised patients (population not defined in the abstract)primaryCunningham 2008median 9.9 months; 40.8% at 12 momedian 9.9 months; 37.7% at 12 mo—
OSAll randomised patients (population not defined in the abstract)exploratoryCunningham 2008median 11.2 monthsmedian 9.9 monthsHR 0.80 (95% CI 0.66–0.97)P=0.02Labelled a secondary analysis in the abstract; progression-free survival and response rates did not differ significantly among the regimens.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
OSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
OS0.860.8–0.99
OS0.920.8–1.1
OS0.80.66–0.97
Illustrative — modelled from reported values, not trial data. OS, primary.
0%25%50%75%100%0510152025Months (modelled)
  • ECF (control)
  • ECX (experimental)
  • EOF (experimental)
  • EOX (experimental)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsECFECXEOFEOX
0100.0%100.0%100.0%100.0%
761.3%61.3%59.3%64.8%
1437.5%37.5%35.2%42.0%
2123.0%23.0%20.9%27.3%
2814.1%14.1%12.4%17.7%
Illustrative — modelled from reported values, not trial data. OS, exploratory.
0%25%50%75%100%0510152025Months (modelled)
  • EOX (experimental)
  • ECF (control)

Median-only curves assume a constant hazard (exponential) and fit plateaus, as seen with some immunotherapies, poorly.

Data table (modelled values)
MonthsEOXECF
0100.0%100.0%
764.8%61.3%
1442.0%37.5%
2127.3%23.0%
2817.7%14.1%
Primary publication: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36-46. PubMedDOI

Appears in

Sources

  1. Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, et al. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008;358(1):36-46.

    PubMedDOI