title: Efficacy and safety of single-agent pertuzumab, a human epidermal receptor dimerization inhibitor, in patients with non small cell lung cancer.
abstract: OBJECTIVE
  Pertuzumab, a first-in-class human epidermal receptor 2 (HER2) dimerization inhibitor, is a humanized monoclonal anti-HER2 antibody that binds HER2's dimerization domain and inhibits HER2 signaling. Based on supporting preclinical studies, we undertook a Phase II trial of pertuzumab in patients with recurrent non-small cell lung cancer (NSCLC).
  
  
  METHODS
  Patients with previously treated NSCLC accessible for core biopsy and naive to HER pathway inhibitors were treated with pertuzumab i.v. once every 3 weeks. Tumor assessments were done at 6 and 12 weeks and then every 3 months thereafter. The primary efficacy end point was overall response rate by Response Evaluation Criteria in Solid Tumors. Measurement of tumor glucose metabolism (SUVmax) by F-18-fluorodeoxyglucose positron emission tomography was used as an exploratory pharmacodynamic marker of drug activity.
  
  
  RESULTS
  Of 43 patients treated with pertuzumab, no responses were seen; 18 of 43 (41.9%) and 9 of 43 (20.9%) patients had stable disease at 6 and 12 weeks, respectively. The median and 3-month progression-free survival rates (PFS) were 6.1 weeks (95% confidence interval, 5.3-11.3 weeks) and 28.4% (95% confidence interval, 14.4-44.2%), respectively. Of 22 patients who underwent F-18-fluorodeoxyglucose positron emission tomography, six (27.3%) had a metabolic response to pertuzumab as evidenced by decreased SUV max. These patients had prolonged PFS (HR = 0.11, log-rank P value = 0.018) compared with the 16 patients who had no metabolic response. Four patients (9.3%) experienced a grade 3/grade 4 adverse event judged related to pertuzumab; none exhibited grade 3/grade 4 cardiac toxicity.
  
  
  CONCLUSIONS
  Pertuzumab is well tolerated as monotherapy. Pharmacodynamic activity correlated with prolonged PFS was detected in a moderate percentage of patients (27.3%). Further clinical development of pertuzumab should focus on rational combinations of pertuzumab with other drugs active in NSCLC.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
authors.forename: Roy S
authors.initials: RS
authors.lastname: Herbst
authors.forename: Angela M
authors.initials: AM
authors.lastname: Davies
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Natale
authors.forename: Thao P
authors.initials: TP
authors.lastname: Dang
authors.forename: Joan H
authors.initials: JH
authors.lastname: Schiller
authors.forename: Linda L
authors.initials: LL
authors.lastname: Garland
authors.forename: Vincent A
authors.initials: VA
authors.lastname: Miller
authors.forename: David
authors.initials: D
authors.lastname: Mendelson
authors.forename: Annick D
authors.initials: AD
authors.lastname: Van den Abbeele
authors.forename: Yulia
authors.initials: Y
authors.lastname: Melenevsky
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: de Vries
authors.forename: David A
authors.initials: DA
authors.lastname: Eberhard
authors.forename: Benjamin
authors.initials: B
authors.lastname: Lyons
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Lutzker
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Johnson
mesh_terms: D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D019281:Dimerization; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000494:pharmacology; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D049268:Positron-Emission Tomography / Q000379:methods; D017434:Protein Structure, Tertiary; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000737:chemistry*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D066246:ErbB Receptors; D019788:Fluorodeoxyglucose F18; D018719:Erb-b2 Receptor Tyrosine Kinases; C485206:pertuzumab