Ramucirumab combined with FOLFOX as front-line therapy for advanced esophageal, gastroesophageal junction, or gastric adenocarcinoma: A randomized, double-blind, multicenter Phase II trial

Harry H. Yoon, J. C. Bendell, F. S. Braiteh, I. Firdaus, P. A. Philip, A. L. Cohn, N. Lewis, D. M. Anderson, E. Arrowsmith, J. D. Schwartz, L. Gao, Y. Hsu, Y. Xu, D. Ferry, S. R. Alberts, Z. A. Wainberg

Research output: Contribution to journalArticlepeer-review

68 Scopus citations

Abstract

Background: We report the first randomized, Phase II trial of ramucirumab, an anti-vascular endothelial growth factor receptor-2 monoclonal antibody, as front-line therapy in patients with advanced adenocarcinoma of the esophagus or gastric/gastroesophageal junction (GEJ). Patients and methods: Patients from the USA with advanced esophageal, gastric, or GEJ adenocarcinoma randomly received (1:1) mFOLFOX6 plus ramucirumab (8 mg/kg) or mFOLFOX6 plus placebo every 2 weeks. The primary end point was progression-free survival (PFS) with 80% power to detect a hazard ratio (HR) of 0.71 (one-sided α = 0.15). Secondary end points included evaluation of response and overall survival (OS); an exploratory ramucirumab exposure- response analysis was undertaken. Results: Of 168 randomized patients, 52% of tumors were located in the stomach/GEJ and 48% in the esophagus. The trial did not meet the primary end point of PFS [6.4 versus 6.7 months, HR 0.98 (95% confidence interval 0.69-1.37)] or the secondary end point of OS (11.7 versus 11.5 months) in the intent-to-treat (ITT) population. Objective response rates (45.2% versus 46.4%) were similar between arms. Most Grade ≥3 toxicities did not differ significantly between arms, yet premature discontinuation of FOLFOX and ramucirumab (for reasons other than progressive disease) was more common among ramucirumab- versus placebo-treated patients. In an exploratory analysis that censored for premature discontinuation, the HR for PFS favored the ramucirumab arm (HR 0.76), particularly in patients with gastric/GEJ cancer. An exploratory exposure-response analysis indicated that patients with higher ramucirumab exposure had longer OS. Conclusion: The addition of ramucirumab to front-line mFOLFOX6 did not improve PFS in the ITT population.

Original languageEnglish (US)
Pages (from-to)2196-2203
Number of pages8
JournalAnnals of Oncology
Volume27
Issue number12
DOIs
StatePublished - 2016

Keywords

  • Esophageal cancer
  • Gastric cancer
  • Gastroesophageal junction
  • Ramucirumab
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Hematology
  • Oncology

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