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

Fred R. Hirsch, Ramaswamy Govindan, Zanete Zvirbule, Fadi Braiteh, Achim Rittmeyer, Cristóbal Belda-Iniesta, Dolores Isla, Thomas Cosgriff, Michelle Boyer, Masamichi Ueda, See Phan, David R. Gandara

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20 Scopus citations

Abstract

We evaluated the effectiveness of onartuzumab plus first-line platinum-doublet chemotherapy in 109 patients with advanced squamous cell non–small-cell lung cancer. The patients were randomized 1:1 to receive onartuzumab or placebo plus paclitaxel/platinum. Onartuzumab did not confer any clinical benefit in the intent-to-treat population or in the MET immunohistochemistry-positive population. These findings are consistent with the published data for onartuzumab in other lung cancer studies. Introduction 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 Methods The 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. Results The 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. Conclusion Studies 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.

Original languageEnglish
Pages (from-to)43-49
Number of pages7
JournalClinical Lung Cancer
Volume18
Issue number1
DOIs
StatePublished - Jan 1 2017

Keywords

  • Immunohistochemistry
  • MET signaling
  • NSCLC
  • Poor prognosis
  • Squamous cell carcinoma

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