BACKGROUND: The phase II YO28252 study (NCT01590719) examined first-line 
onartuzumab plus mFOLFOX6 in patients with metastatic, human epidermal growth 
factor receptor 2-negative adenocarcinoma of the stomach or gastroesophageal 
junction. MET immunohistochemistry expression as a biomarker of onartuzumab 
activity was also examined.
PATIENTS AND METHODS: Patients were randomized 1:1 to receive standard mFOLFOX6 
plus onartuzumab (10 mg/kg) or placebo in 2-week cycles for 12 cycles, followed 
by onartuzumab or placebo until disease progression. Coprimary endpoints were 
progression-free survival (PFS) in intent-to-treat (ITT) and MET-positive 
populations. The target hazard ratio (HR) was 0.70 for patients in the ITT group 
and 0.60 in the MET-positive population. Secondary endpoints were overall 
survival (OS), overall response rate (ORR), and safety.
RESULTS: Overall, 123 patients were enrolled (n = 62 onartuzumab, n = 61 
placebo). Median PFS was 6.77 versus 6.97 months for onartuzumab versus placebo, 
respectively (HR, 1.08; 95% confidence interval [CI], 0.71-1.63; p = .71). In 
the MET-positive population, median PFS was 5.95 versus 6.80 months, onartuzumab 
versus placebo (HR, 1.38; 95% CI, 0.60-3.20; p = .45). Median OS was 10.61 
months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64-1.75; p 
= .83). In the MET-positive population, median OS was 8.51 versus 8.48 months 
for onartuzumab versus placebo, respectively (HR, 1.12, 95% CI, 0.45-2.78; p = 
.80). ORR was 60.5% for the onartuzumab group and 57.1% for placebo. Grade 3-5 
adverse events (AEs) were seen in 88.3% of patients receiving onartuzumab and in 
78.3% of patients receiving placebo, with serious AEs in 55% and 40%, 
respectively.
CONCLUSION: The addition of onartuzumab to mFOLFOX6 in gastric cancer did not 
improve efficacy in an unselected population or in a MET 
immunohistochemistry-positive population.
IMPLICATIONS FOR PRACTICE: The YO28252 study demonstrated that the addition of 
the anti-MET agent onartuzumab to mFOLFOX6 for treatment of gastric cancer did 
not improve efficacy in an overall study population or those selected for 
positive MET status by immunohistochemistry. This highlights the importance of 
correctly selecting biomarkers for targeted therapies. A multivariate analysis 
suggested that MET positivity may still be prognostic for worse median overall 
survival in gastric cancer; therefore, it is important to continue investigation 
into the optimal approach to inhibit MET signaling in gastric cancer.