Randomized controlled phase II trial of S-1 maintenance therapy in Caucasian population with metastatic esophagogastric cancer– the multinational MATEO study

Abstract

Background: Chemotherapy including a fluoropyrimidine and a platinum compound is still the mainstay for the majority of patients with esophagogastric adenocarcinoma. The optimal duration of firstline chemotherapy is unknown. In most clinical trials therapy is given until tumor progression or dose-limiting toxicity. Maintenance concepts have been established in other tumor types but not in esophagogastric cancer. S-1 is an oral fluoropyrimidine with proven efficacy in metastatic esophagogastric cancer. Given as a monotherapy S-1 showed a beneficial toxicity pattern. Trial design: MATEO is a randomized, multinational, phase II trial in patients with previously untreated, Her-2 negative metastatic esophagogastric adenocarcinoma. After having completed, without tumor progression, a 12-week induction chemotherapy (including a platinum compound, a fluoropyrimidine with or without a taxane or an anthracycline), 297 patients will be randomized in a 2:1 allocation to receive S-1 monotherapy or to continue the same polychemotherapy until progression or limiting toxicities. Patients will be stratified according to the response to the induction therapy at the time of randomization (CR/PR vs. SD) and the polychemotherapy used during the induction phase (doublet vs. triplet regimen). The primary endpoint is overall survival, secondary endpoints include progression-free survival, safety and quality of life. Sample size estimation is based on the statistical goal to allow for a first formal within-study comparison of efficacy and to exclude any increase of risk of death due to de-escalation with S-1 by more than 33% compared to continuation of polychemotherapy. A non-inferiority testing approach on a 10% significance level will be used. Tissue- and blood based translational analysis will focus on the identification of a subgroup with a sustained benefit from S-1 based maintenance therapy. This trial is lead by the Gastric Cancer Group and Young Medical Oncologists group of the AIO (Arbeitsgemeinschaft Internistische Onkologie) with the participation of sites in 6 European countries.