A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction. (8th July 2016)

• Record Type: Journal Article
• 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
• Is Part Of: Oncologist. Volume 21:Number 9(2016)
• Page Start: 1085
• Page End: 1090
• Publication Date: 2016-07-08
• Subjects: MET -- Gastric cancer -- Chemotherapy -- Onartuzumab -- HER2-negative -- First line; Oncology -- Periodicals; Tumors -- Periodicals; Cancérologie -- Périodiques; Tumeurs -- Périodiques; Oncology; Tumors; Neoplasms; Electronic journals; Periodicals; Periodicals; 616.994
• DOI: 10.1634/theoncologist.2016-0038
• Languages: English
• ISSNs: 1083-7159

Abstract

Abstract : Background: The phase II YO28252 study (01590719 ) 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. Abstract : Patients with metastatic, HER2-negative adenocarcinoma of the stomach or gastroesophageal junction, including those with MET-positive immunohistochemistry, were randomized 1:1 to receive standard mFOLFOX6 plus onartuzumab or placebo, followed by onartuzumab or placebo until disease progression. Median progression-free and overall survival did not differ between groups. The addition of onartuzumab to mFOLFOX6 in gastric cancer did not improve efficacy.