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 and0.60 in the MET-positive population. Secondary end points were overall survival (OS), overall response rate (ORR), and safety. Results. Overall, 123patients were enrolled (n562onartuzumab, n 5 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 5 = 71). In the MET-positive population, median PFS was 5.95 versus 6.80months, onartuzumab versus placebo (HR, 1.38; 95% CI, 0.60–3.20; p5.45).Median OS was 10.61 months for onartuzumab versus 11.27 months for placebo) (HR, 1.06, 0.64–1.75; p 5 =.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 5=.80). ORR was 60.5% for the onartuzumab group and 57.1%for placebo. Grade3–5adver see vents (AEs) wereseenin 88.3% of patients receiving onartuzumab and in 78.3% of patients receiving placebo, with serious AEs in 55% and 40%, respectively. Conclusion. Theaddition of onartuzumab to mFOLFOX6 ingastric cancer did not improve efficacy in an unselected population orin a MET immunohistochemistry-positive population.
All Science Journal Classification (ASJC) codes
- Cancer Research