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

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.

CLINICALTRIALSGOV IDENTIFIER:

NCT01246960.

• Authors: H 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
• Journal: Annals of oncology : official journal of the European Society for Medical Oncology (Ann Oncol) Vol. 27 Issue 12 Pg. 2196-2203 (12 2016) ISSN: 1569-8041 [Electronic] England
• PMID: 27765757 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, N.I.H., Extramural)
• Copyright: © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: [email protected].

Chemical References

• Antibodies, Monoclonal
• Antibodies, Monoclonal, Humanized
• Organoplatinum Compounds
• Leucovorin
• Fluorouracil

Topics

• Adenocarcinoma (drug therapy, pathology)
• Adult
• Aged
• Antibodies, Monoclonal (administration & dosage, adverse effects)
• Antibodies, Monoclonal, Humanized
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage)
• Disease-Free Survival
• Double-Blind Method
• Esophageal Neoplasms (drug therapy, pathology)
• Esophagogastric Junction (drug effects)
• Female
• Fluorouracil (administration & dosage)
• Humans
• Kaplan-Meier Estimate
• Leucovorin (administration & dosage)
• Male
• Middle Aged
• Organoplatinum Compounds (administration & dosage)
• Stomach Neoplasms (drug therapy)
• Treatment Outcome
• Ramucirumab