title: Results From the Phase III Randomized Trial of Onartuzumab Plus Erlotinib Versus Erlotinib in Previously Treated Stage IIIB or IV Non-Small-Cell Lung Cancer: METLung.
abstract: Purpose The phase III OAM4971g study (METLung) examined the efficacy and safety of onartuzumab plus erlotinib in patients with locally advanced or metastatic non-small-cell lung cancer selected by MET immunohistochemistry whose disease had progressed after treatment with a platinum-based chemotherapy regimen. Patients and Methods Patients were randomly assigned at a one-to-one ratio to receive onartuzumab (15 mg/kg intravenously on day 1 of each 21-day cycle) plus daily oral erlotinib 150 mg or intravenous placebo plus daily oral erlotinib 150 mg. The primary end point was overall survival (OS) in the intent-to-treat population. Secondary end points included median progression-free survival, overall response rate, biomarker analysis, and safety. Results A total of 499 patients were enrolled (onartuzumab, n = 250; placebo, n = 249). Median OS was 6.8 versus 9.1 months for onartuzumab versus placebo (stratified hazard ratio [HR], 1.27; 95% CI, 0.98 to 1.65; P = .067), with a greater number of deaths in the onartuzumab arm (130 [52%] v 114 [46%]). Median progression-free survival was 2.7 versus 2.6 months (stratified HR, 0.99; 95% CI, 0.81 to 1.20; P = .92), and overall response rate was 8.4% and 9.6% for onartuzumab versus placebo, respectively. Exploratory analyses using MET fluorescence in situ hybridization status and gene expression showed no benefit for onartuzumab; patients with EGFR mutations showed a trend toward shorter OS with onartuzumab treatment (HR, 4.68; 95% CI, 0.97 to 22.63). Grade 3 to 5 adverse events were reported by 56.0% and 51.2% of patients, with serious AEs in 33.9% and 30.7%, for experimental versus control arms, respectively. Conclusion Onartuzumab plus erlotinib did not improve clinical outcomes, with shorter OS in the onartuzumab arm, compared with erlotinib in patients with MET-positive non-small-cell lung cancer.
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: David R
authors.initials: DR
authors.lastname: Spigel
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Edelman
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Kenneth
authors.initials: K
authors.lastname: O'Byrne
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Luis
authors.initials: L
authors.lastname: Paz-Ares
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Simonetta
authors.initials: S
authors.lastname: Mocci
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: See
authors.initials: S
authors.lastname: Phan
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: David S
authors.initials: DS
authors.lastname: Shames
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Dustin
authors.initials: D
authors.lastname: Smith
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Wei
authors.initials: W
authors.lastname: Yu
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Virginia E
authors.initials: VE
authors.lastname: Paton
authors.affiliation: David R. Spigel, Sarah Cannon Research Institute, Nashville, TN; Martin J. Edelman, University of Maryland Greenebaum Cancer Center, Baltimore, MD; Kenneth O'Byrne, Queensland University of Technology, Brisbane, Queensland, Australia; Luis Paz-Ares, Hospital Universitario Doce de Octubre and Centro Nacional de Investigaciones Oncológicas, Madrid, Spain; Simonetta Mocci, See Phan, David S. Shames, Dustin Smith, Wei Yu, and Virginia E. Paton, Genentech, South San Francisco, CA; and Tony Mok, Chinese University of Hong Kong, Hong Kong, Special Administrative Region, People's Republic of China.
authors.forename: Tony
authors.initials: T
authors.lastname: Mok
mesh_terms: D061605:Administration, Intravenous; D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D000069347:Erlotinib Hydrochloride / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000911:Antibodies, Monoclonal; D047428:Protein Kinase Inhibitors; D000069347:Erlotinib Hydrochloride; C584058:onartuzumab