IMPORTANCE: Dysregulation of the mesenchymal-epithelial transition (MET) 
signaling pathway is associated with poor prognosis in gastroesophageal 
adenocarcinoma (GEC). We report results of METGastric, a phase 3 trial of the 
MET inhibitor onartuzumab plus standard first-line chemotherapy for human 
epidermal growth factor receptor 2 (HER2)-negative, MET-positive, advanced GEC.
OBJECTIVE: To determine whether the addition of onartuzumab to first-line 
fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) improves efficacy compared 
with mFOLFOX6 plus placebo in HER2-negative, MET-positive GEC.
DESIGN, SETTING, AND PARTICIPANTS: Randomized, double-blind, multicenter trial 
conducted from November 2012 to March 2014. Patients were 18 years or older with 
an adenocarcinoma of the stomach or gastroesophageal junction with metastatic 
disease not amenable for curative therapy. Tumor samples were centrally tested 
for MET expression using Ventana anti-Total c-MET (SP44) rabbit monoclonal 
antibody, HER2 status, and Lauren histologic subtype. MET-positive tumors were 
defined as at least 50% of tumor cells showing weak, moderate, and/or strong 
staining intensity (MET 1+/2+/3+, respectively) by immunohistochemistry.
INTERVENTIONS: Patients with HER2-negative, MET-positive GEC were enrolled and 
randomized 1:1 to receive mFOLFOX6 with or without onartuzumab (10 mg/kg).
MAIN OUTCOMES AND MEASURES: Co-primary end points: overall survival in the 
intent-to-treat (ITT) population and in patients with MET 2+/3+ GEC. Secondary 
end points: progression-free survival (PFS), overall response rate (ORR), and 
safety.
RESULTS: Enrollment was stopped early due to sponsor decision, which was agreed 
with an independent data monitoring committee. At the data cutoff (April 25, 
2014) there were 562 patients in the ITT population (n = 283 placebo plus 
mFOLFOX6 [median age, 58 y; 65% male]; n = 279 onartuzumab plus mFOLFOX6 [median 
age, 60 y; 67% male]); 109 (38.5%) and 105 (37.6%) of the ITT population were 
MET 2+/3+, respectively. Addition of onartuzumab to mFOLFOX6 did not 
significantly improve OS, PFS, or ORR vs placebo plus mFOLFOX6 in the ITT (OS 
hazard ratio [HR], 0.82; 95% CI, 0.59-1.15; P = .24; PFS HR, 0.90; 95% CI, 
0.71-1.16; P = .43; ORR, 46.1% vs 40.6%) or MET 2+/3+ populations (OS HR, 0.64; 
95% CI, 0.40-1.03; P = .06; PFS HR, 0.79; 95% CI, 0.54-1.15; P = .22; ORR, 53.8% 
vs 44.6%). Safety was as expected for onartuzumab.
CONCLUSIONS AND RELEVANCE: Addition of onartuzumab to first-line mFOLFOX6 did 
not significantly improve clinical benefits in the ITT or MET 2+/3+ populations.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01662869.