Heather Wakelee1, Zanete Zvirbule2, Filippo De Braud3, C Daniel Kingsley4, Tarek Mekhail5, Thomas Lowe6, Wolfgang Schütte7, Hervé Lena8, William Lawler9, Fadi Braiteh10, Thomas Cosgriff11, Diego Kaen12, Michelle Boyer13, Jessie Hsu14, See Phan14, Silvia Novello15. 1. Division of Oncology, Department of Medicine, Stanford University, Stanford, CA. Electronic address: hwakelee@stanford.edu. 2. Medical Oncology Department, Riga Eastern Clinical University Hospital, Latvian Oncology Center, Riga, Latvia. 3. Medical Oncology Department, National Cancer Institute of Milan, Milan, Italy. 4. Clearview Cancer Institute, Huntsville, AL. 5. Department of Hematology/Oncology, Florida Hospital, Orlando, FL. 6. Department of Medical Oncology, Cancer Care Associates Medical Group, Inc, Redondo Beach, CA. 7. Department of Internal Medicine II, Martha-Maria Krankenhaus Halle-Dölau gGmbH, Halle, Germany. 8. Pneumology Service, Hôpital Pontchaillou, Rennes, France. 9. St Jude Heritage Medical Group, Fullerton, CA. 10. Department of Medical Oncology, Comprehensive Cancer Centers of Nevada, Henderson, NV. 11. Division of Hematology/Oncology, Crescent City Research Consortium, Marrero, LA. 12. Centro Oncologico Riojano Integral (CORI), La Rioja, Argentina. 13. Department of Clinical Science, F. Hoffmann-La Roche Ltd, Welwyn Garden City, UK. 14. Biostatistics Department, Product Development Oncology, Genentech Inc., San Francisco, CA. 15. Department of Oncology, AOU San Luigi-Orbassano, University of Turin, Turin, Italy.
Abstract
BACKGROUND:Onartuzumab is a monovalent monoclonal antibody that binds with the extracellular domain of the MET receptor. Given the role of MET in non-small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to first-line chemotherapy efficacy in non-squamous NSCLC. METHODS:Patients with untreated stage IIIB/IV non-squamous NSCLC, stratified by MET diagnostic status, were randomized to receive onartuzumab (15 mg/kg intravenously every 3 weeks) or placebo in combination with either paclitaxel/platinum/bevacizumab (bevacizumab cohort), or in combination with platinum/pemetrexed (pemetrexed cohort) with maintenance bevacizumab or pemetrexed and onartuzumab/placebo as appropriate. Co-primary endpoints of this phase II study were progression-free survival (PFS) in all patients and in MET+ patients (2+/3+), defined by the Ventana immunohistochemistry assay; secondary endpoints included overall survival (OS), objective response rate (ORR), safety, and pharmacokinetics. RESULTS: Efficacy data were available for 139 and 120 patients in the bevacizumab and pemetrexed cohorts, respectively. No benefit was seen in the PFS endpoint in the intent-to treat population of either cohort, but was numerically worse in the onartuzumab arm of the MET+ subgroup of the bevacizumab cohort. The onartuzumab and placebo arms had similar ORR and OS results in both cohorts. A higher incidence of some adverse events was observed with onartuzumab versus placebo, including peripheral edema (30% vs. 3%, bevacizumab cohort; 48% vs. 14%, pemetrexed cohort) and venous thromboembolic events (bevacizumab cohort only, 15% vs. 6%). CONCLUSION:Onartuzumab does not appear to provide any additional clinical benefit when given in combination with current first-line standard-of-care chemotherapy for non-squamous NSCLC.
RCT Entities:
BACKGROUND:Onartuzumab is a monovalent monoclonal antibody that binds with the extracellular domain of the MET receptor. Given the role of MET in non-small-cell lung cancer (NSCLC), we investigated whether onartuzumab added to first-line chemotherapy efficacy in non-squamous NSCLC. METHODS:Patients with untreated stage IIIB/IV non-squamous NSCLC, stratified by MET diagnostic status, were randomized to receive onartuzumab (15 mg/kg intravenously every 3 weeks) or placebo in combination with either paclitaxel/platinum/bevacizumab (bevacizumab cohort), or in combination with platinum/pemetrexed (pemetrexed cohort) with maintenance bevacizumab or pemetrexed and onartuzumab/placebo as appropriate. Co-primary endpoints of this phase II study were progression-free survival (PFS) in all patients and in MET+ patients (2+/3+), defined by the Ventana immunohistochemistry assay; secondary endpoints included overall survival (OS), objective response rate (ORR), safety, and pharmacokinetics. RESULTS: Efficacy data were available for 139 and 120 patients in the bevacizumab and pemetrexed cohorts, respectively. No benefit was seen in the PFS endpoint in the intent-to treat population of either cohort, but was numerically worse in the onartuzumab arm of the MET+ subgroup of the bevacizumab cohort. The onartuzumab and placebo arms had similar ORR and OS results in both cohorts. A higher incidence of some adverse events was observed with onartuzumab versus placebo, including peripheral edema (30% vs. 3%, bevacizumab cohort; 48% vs. 14%, pemetrexed cohort) and venous thromboembolic events (bevacizumab cohort only, 15% vs. 6%). CONCLUSION:Onartuzumab does not appear to provide any additional clinical benefit when given in combination with current first-line standard-of-care chemotherapy for non-squamous NSCLC.
Authors: Aiwu Ruth He; Roger B Cohen; Crystal S Denlinger; Ashwin Sama; Ariel Birnbaum; Jimmy Hwang; Takami Sato; Nancy Lewis; Michelle Mynderse; Michele Niland; Jennifer Giles; Johan Wallin; Brian Moser; Wei Zhang; Richard Walgren; Elizabeth R Plimack Journal: Oncologist Date: 2019-03-04
Authors: Alessia E Russo; Domenico Priolo; Giovanna Antonelli; Massimo Libra; James A McCubrey; Francesco Ferraù Journal: Lung Cancer (Auckl) Date: 2017-12-14