Efficacy and Safety of Onartuzumab in Combination With First-Line Bevacizumab- or Pemetrexed-Based Chemotherapy Regimens in Advanced Non-Squamous Non-Small-Cell Lung Cancer

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• 作者：Heather Wakelee¹ ; ^{hwakelee@stanford.edu} ; Zanete Zvirbule² ; Filippo De Braud³ ; C. Daniel Kingsley⁴ ; Tarek Mekhail⁵ ; Thomas Lowe⁶ ; Wolfgang Schü ; tte⁷ ; Hervé ; Lena⁸ ; William Lawler⁹ ; Fadi Braiteh¹⁰ ; Thomas Cosgriff¹¹ ; Diego Kaen¹² ; Michelle Boyer¹³ ; Jessie Hsu¹⁴ ; See Phan¹⁴ ; Silvia Novello¹⁵
• 关键词：Biomarkers ; Combination therapy ; MET ; Phase II clinical trial ; Progression-free survival
• 刊名：Clinical Lung Cancer
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：18
• 期：1
• 页码：50-59
• 全文大小：356 K
• 卷排序：18

文摘

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.MethodsPatients 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.ResultsEfficacy 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%).ConclusionOnartuzumab 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.