Umbrella strategy with systemic and intraperitoneal chemotherapy versus systemic chemotherapy in patients with advanced gastric cancer: a multicenter, randomized Phase III clinical trial

Abstract

Abstract Background We have developed a tridirectional regimen combining intraperitoneal, intravenous, and oral chemotherapy as a treatment for patients with advanced gastric cancer and individualized these chemotherapeutics according to mRNA expression. This multicenter Phase III umbrella study compared the efficacy and safety of individualized tridirectional intraperitoneal and systemic chemotherapy with that of standard systemic chemotherapy. Methods BRCA1/TOPO1 mRNA expression was examined in all enrolled patients. The patients were then randomized in a ratio of 3:1 to an individualized arm and a control arm. Patients in the control arm received systemic intravenous/oral chemotherapy, whereas those in the individualized arm received sensitive chemotherapeutics selected from oxaliplatin/cisplatin/docetaxel/irinotecan/S-1 according to their BRCA1/TOPO1 mRNA expression and received individualized tridirectional intraperitoneal/intravenous/oral chemotherapy. The primary endpoint was progression-free survival and the secondary endpoints were response rate, overall survival, and safety. Results Overall, 233 of 240 patients enrolled between August 2014 and December 2016 were included in the efficacy analysis. Baseline patient characteristics were balanced between the two arms. The objective response rate was 33.9% in the control arm and 49.1% in the individualized arm (P = 0.039). In the control and individualized arms, median progression-free survival was 5.9 months and 8.0 months, respectively (hazard ratio 0.521, 95% confidence interval 0.362–0.750, P = 0.0005) and median overall survival was 13.5 months and 16.4 months, respectively (hazard ratio 0.684, 95% confidence interval 0.474–0.988, P = 0.0430). Both regimens were tolerable. Conclusion The primary analysis demonstrated the statistical superiority of this tridirectional individualized regimen and suggests that this regimen has clinical efficacy in patients with advanced gastric cancer. Trial registration Chinese Clinical Trial Registry (chictr.org.cn) Identifier: ChiCTR-IPR-15006201.