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

Heather Wakelee, Zanete Zvirbule, Filippo De Braud, C. Daniel Kingsley, Tarek Mekhail, Thomas Lowe, Wolfgang Schütte, Hervé Lena, William Lawler, Fadi Braiteh, Thomas Cosgriff, Diego Kaen, Michelle Boyer, Jessie Hsu, See Phan, Silvia Novello

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalClinical Lung Cancer
DOIs
Publication statusPublished - 2017

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Pemetrexed
Non-Small Cell Lung Carcinoma
Safety
Drug Therapy
Placebos
Platinum
Disease-Free Survival
Bevacizumab
onartuzumab
Standard of Care
Paclitaxel
Edema
Survival Rate
Pharmacokinetics
Immunohistochemistry
Monoclonal Antibodies
Maintenance

Keywords

  • Biomarkers
  • Combination therapy
  • MET
  • Phase II clinical trial
  • Progression-free survival

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

Cite this

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. / Wakelee, Heather; Zvirbule, Zanete; De Braud, Filippo; Kingsley, C. Daniel; Mekhail, Tarek; Lowe, Thomas; Schütte, Wolfgang; Lena, Hervé; Lawler, William; Braiteh, Fadi; Cosgriff, Thomas; Kaen, Diego; Boyer, Michelle; Hsu, Jessie; Phan, See; Novello, Silvia.

In: Clinical Lung Cancer, 2017.

Research output: Contribution to journalArticle

Wakelee, H, Zvirbule, Z, De Braud, F, Kingsley, CD, Mekhail, T, Lowe, T, Schütte, W, Lena, H, Lawler, W, Braiteh, F, Cosgriff, T, Kaen, D, Boyer, M, Hsu, J, Phan, S & Novello, S 2017, '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', Clinical Lung Cancer. https://doi.org/10.1016/j.cllc.2016.09.013
Wakelee, Heather ; Zvirbule, Zanete ; De Braud, Filippo ; Kingsley, C. Daniel ; Mekhail, Tarek ; Lowe, Thomas ; Schütte, Wolfgang ; Lena, Hervé ; Lawler, William ; Braiteh, Fadi ; Cosgriff, Thomas ; Kaen, Diego ; Boyer, Michelle ; Hsu, Jessie ; Phan, See ; Novello, Silvia. / 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. In: Clinical Lung Cancer. 2017.
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title = "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",
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.",
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author = "Heather Wakelee and Zanete Zvirbule and {De Braud}, Filippo and Kingsley, {C. Daniel} and Tarek Mekhail and Thomas Lowe and Wolfgang Sch{\"u}tte and Herv{\'e} Lena and William Lawler and Fadi Braiteh and Thomas Cosgriff and Diego Kaen and Michelle Boyer and Jessie Hsu and See Phan and Silvia Novello",
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T1 - 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

AU - Wakelee, Heather

AU - Zvirbule, Zanete

AU - De Braud, Filippo

AU - Kingsley, C. Daniel

AU - Mekhail, Tarek

AU - Lowe, Thomas

AU - Schütte, Wolfgang

AU - Lena, Hervé

AU - Lawler, William

AU - Braiteh, Fadi

AU - Cosgriff, Thomas

AU - Kaen, Diego

AU - Boyer, Michelle

AU - Hsu, Jessie

AU - Phan, See

AU - Novello, Silvia

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Biomarkers

KW - Combination therapy

KW - MET

KW - Phase II clinical trial

KW - Progression-free survival

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