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Clinical Trial
. 2016 Dec;27(12):2196-2203.
doi: 10.1093/annonc/mdw423. Epub 2016 Oct 20.

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

H H Yoon  1 , J C Bendell  2 , F S Braiteh  3 , I Firdaus  4 , P A Philip  5 , A L Cohn  6 , N Lewis  7 , D M Anderson  8 , E Arrowsmith  9 , J D Schwartz  10 , L Gao  10 , Y Hsu  10 , Y Xu  10 , D Ferry  10 , S R Alberts  11 , Z A Wainberg  12
Affiliations
Clinical Trial

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

H H Yoon et al. Ann Oncol. 2016 Dec.

Erratum in

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.

Keywords: esophageal cancer; gastric cancer; gastroesophageal junction; ramucirumab; vascular endothelial growth factor.

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Figure 1
Figure 1
CONSORT diagram. ITT, intent to treat.
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Figure 2
Figure 2
The Kaplan–Meier analysis of efficacy in the intent-to-treat (ITT) population. Progression-free survival (A) and overall survival (B).
Figure 3
Figure 3
Forest plot for subgroup analysis of progression-free survival (PFS) in the ITT population with and without censoring for premature treatment discontinuation. PFS in the ITT population (A) and PFS in the ITT population after censoring for premature treatment discontinuation (B). CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; GEJ, gastroesophageal junction; HR, hazard ratio; ITT, intent to treat; PBO, placebo; RAM, ramucirumab.
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Supplementary Data
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Supplementary Data
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Comment in

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