Efficacy and Safety Results From a Phase II, Placebo-Controlled Study of Onartuzumab Plus First-Line Platinum-Doublet Chemotherapy for Advanced Squamous Cell Non-Small-Cell Lung Cancer

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• 作者：Fred R. Hirsch¹ ; ^{Fred.Hirsch@ucdenver.edu} ; Ramaswamy Govindan² ; Zanete Zvirbule³ ; Fadi Braiteh⁴ ; Achim Rittmeyer⁵ ; Crist&oacute ; bal Belda-Iniesta⁶ ; Dolores Isla⁷ ; Thomas Cosgriff⁸ ; Michelle Boyer⁹ ; Masamichi Ueda¹⁰ ; See Phan¹¹ ; David R. Gandara¹²
• 关键词：Immunohistochemistry ; MET signaling ; NSCLC ; Poor prognosis ; Squamous cell carcinoma
• 刊名：Clinical Lung Cancer
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：18
• 期：1
• 页码：43-49
• 全文大小：609 K
• 卷排序：18

文摘

The treatment options for squamous cell non–small-cell lung cancer (NSCLC) are limited. We assessed the efficacy and safety of onartuzumab plus platinum-doublet chemotherapy in previously untreated advanced squamous cell NSCLC.Patients and MethodsThe patients were randomized to receive onartuzumab plus paclitaxel plus carboplatin/cisplatin (n = 55) or placebo plus paclitaxel plus carboplatin/cisplatin (n = 54). Randomization was stratified by MET diagnostic status: MET immunohistochemistry (IHC)-positive (MET IHC 3+/2+) or MET IHC-negative (MET IHC 1+/0). The co-primary endpoints were investigator-assessed progression-free survival in the intent-to-treat and the MET IHC+ populations.ResultsThe risk of disease progression or death was similar between the 2 treatment arms in both the intent-to-treat (stratified hazard ratio, 0.95; 95% confidence interval, 0.63-1.43) and MET IHC+ populations (unstratified hazard ratio, 1.27; 95% confidence interval, 0.69-2.32). Comparable results were obtained for overall survival and the objective response rate. In all safety-evaluable patients, the grade 3 to 5 adverse events occurring at a > 5% greater incidence in the onartuzumab-containing versus the placebo-containing arm were neutropenia (14.8% vs. 5.8%) and pulmonary embolism (5.6% vs. 0%). Eight patients died as a result of adverse events: 1 case each of pneumonitis, pneumonia, cardiac failure, and unexplained death in the onartuzumab arm and 1 case each of hemorrhage, cardiac arrest, hemoptysis, and febrile neutropenia in the placebo arm.ConclusionStudies using alternative assays of MET activation might help to clarify the role of onartuzumab. However, with the lack of clinical activity seen in the present study, the development of onartuzumab for squamous cell NSCLC will not be pursued further.