Please use this identifier to cite or link to this item:
Title: A randomized phase II study of FOLFOX with or without the MET inhibitor onartuzumab in advanced adenocarcinoma of the stomach and gastroesophageal junction
Austin Authors: Shah, Manish A;Cho, Jae-Yong;Tan, Iain B;Tebbutt, Niall C ;Yen, Chia-Jui;Kang, Alice;Shames, David S;Bu, Lilian;Kang, Yoon-Koo
Affiliation: Weill Cornell Medicine Center for Advanced Digestive Care, New York-Presbyterian Hospital, New York, NY, USA
Severance Hospital (Gangnam), Seoul, South Korea
National Cancer Centre, Singapore
Austin Health, Heidelberg, Victoria, Australia
National Cheng Kung University Hospital, Tainan City, Taiwan, Republic of China
Roche Product Development in Asia Pacific, Shanghai, People’s Republic of China
Oncology Biomarker Development, Genentech Inc., South San Francisco, CA, USA
Asan Medical Center, University of Ulsan, Seoul, South Korea
Issue Date: Sep-2016
Date: 2016-07-08
Publication information: The Oncologist 2016; 21(9): 1085-1090
Abstract: 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% CO, 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.
DOI: 10.1634/theoncologist.2016-0038
Journal: The Oncologist
PubMed URL:
Type: Journal Article
Subjects: Chemotherapy
First line
Gastric cancer
Appears in Collections:Journal articles

Show full item record

Page view(s)

checked on Apr 19, 2024

Google ScholarTM


Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.