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A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction

Authors
 MANISH A. SHAH  ;  JAE-YONG CHO  ;  IAIN B. TAN  ;  NIALL C. TEBBUTT  ;  CHIA-JUI YEN  ;  ALICE KANG  ;  DAVID S. SHAMES  ;  LILIAN BU  ;  YOON-KOO KANG 
Citation
 Oncologist, Vol.21(9) : 1085-1090, 2016 
Journal Title
 Oncologist 
ISSN
 1083-7159 
Issue Date
2016
MeSH
Adenocarcinoma/drug therapy* ; Adenocarcinoma/genetics ; Adenocarcinoma/pathology ; Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal/administration & dosage* ; Antibodies, Monoclonal/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/administration & dosage* ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Disease-Free Survival ; Esophageal Neoplasms/drug therapy* ; Esophageal Neoplasms/genetics ; Esophageal Neoplasms/pathology ; Esophagogastric Junction/drug effects ; Esophagogastric Junction/pathology ; Female ; Fluorouracil/administration & dosage ; Humans ; Leucovorin/administration & dosage ; Male ; Middle Aged ; Molecular Targeted Therapy ; Organoplatinum Compounds/administration & dosage ; Proto-Oncogene Proteins c-met/antagonists & inhibitors* ; Proto-Oncogene Proteins c-met/genetics ; Stomach Neoplasms/drug therapy* ; Stomach Neoplasms/pathology
Keywords
Chemotherapy ; First line ; Gastric cancer ; HER2-negative ; MET ; Onartuzumab
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% 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.
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/165669
Files in This Item:
T999900228.pdf Download
DOI
10.1634/theoncologist.2016-0038
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
Yonsei Authors
이동준(Lee, Dong Jun)
이승현(Lee, Seung Hyun) ORCID logo https://orcid.org/0000-0001-7549-9430
한재현(Han, Jae Hyun)
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