PMID- 27401892 OWN - NLM STAT- MEDLINE DCOM- 20180105 LR - 20220330 IS - 1549-490X (Electronic) IS - 1083-7159 (Print) IS - 1083-7159 (Linking) VI - 21 IP - 9 DP - 2016 Sep TI - A Randomized Phase II Study of FOLFOX With or Without the MET Inhibitor Onartuzumab in Advanced Adenocarcinoma of the Stomach and Gastroesophageal Junction. PG - 1085-90 LID - 10.1634/theoncologist.2016-0038 [doi] AB - 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. CI - (c)AlphaMed Press. FAU - Shah, Manish A AU - Shah MA AD - Weill Cornell Medicine Center for Advanced Digestive Care, New York-Presbyterian Hospital, New York, New York, USA. FAU - Cho, Jae-Yong AU - Cho JY AD - Severance Hospital (Gangnam), Seoul, Republic of Korea. FAU - Tan, Iain B AU - Tan IB AD - National Cancer Centre, Singapore. FAU - Tebbutt, Niall C AU - Tebbutt NC AD - Austin Health, Heidelberg, Australia. FAU - Yen, Chia-Jui AU - Yen CJ AD - National Cheng Kung University Hospital, Tainan City, Taiwan, Republic of China. FAU - Kang, Alice AU - Kang A AD - Roche Product Development in Asia Pacific, Shanghai, People's Republic of China. FAU - Shames, David S AU - Shames DS AD - Oncology Biomarker Development, Genentech Inc., South San Francisco, California, USA. FAU - Bu, Lilian AU - Bu L AD - Roche Product Development in Asia Pacific, Shanghai, People's Republic of China. FAU - Kang, Yoon-Koo AU - Kang YK AD - Asan Medical Center, University of Ulsan, Seoul, Republic of Korea ykkang@amc.seoul.kr. LA - eng SI - ClinicalTrials.gov/NCT01590719 PT - Clinical Trial, Phase II PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20160708 PL - England TA - Oncologist JT - The oncologist JID - 9607837 RN - 0 (Antibodies, Monoclonal) RN - 0 (Organoplatinum Compounds) RN - EC 2.7.10.1 (MET protein, human) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - MS1J9720WC (onartuzumab) RN - Q573I9DVLP (Leucovorin) RN - U3P01618RT (Fluorouracil) RN - Adenocarcinoma Of Esophagus RN - Folfox protocol SB - IM MH - Adenocarcinoma/*drug therapy/genetics/pathology MH - Adult MH - Aged MH - Aged, 80 and over MH - Antibodies, Monoclonal/*administration & dosage/adverse effects MH - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/adverse effects MH - Disease-Free Survival MH - Esophageal Neoplasms/*drug therapy/genetics/pathology MH - Esophagogastric Junction/drug effects/pathology MH - Female MH - Fluorouracil/administration & dosage MH - Humans MH - Leucovorin/administration & dosage MH - Male MH - Middle Aged MH - Molecular Targeted Therapy MH - Organoplatinum Compounds/administration & dosage MH - Proto-Oncogene Proteins c-met/*antagonists & inhibitors/genetics MH - Stomach Neoplasms/*drug therapy/pathology PMC - PMC5016069 OTO - NOTNLM OT - Chemotherapy OT - First line OT - Gastric cancer OT - HER2-negative OT - MET OT - Onartuzumab EDAT- 2016/07/13 06:00 MHDA- 2018/01/06 06:00 PMCR- 2017/09/01 CRDT- 2016/07/13 06:00 PHST- 2016/02/03 00:00 [received] PHST- 2016/05/17 00:00 [accepted] PHST- 2016/07/13 06:00 [entrez] PHST- 2016/07/13 06:00 [pubmed] PHST- 2018/01/06 06:00 [medline] PHST- 2017/09/01 00:00 [pmc-release] AID - theoncologist.2016-0038 [pii] AID - T1638 [pii] AID - 10.1634/theoncologist.2016-0038 [doi] PST - ppublish SO - Oncologist. 2016 Sep;21(9):1085-90. doi: 10.1634/theoncologist.2016-0038. Epub 2016 Jul 8.