title: Human epidermal growth factor receptor 2 (HER2) extracellular domain levels are associated with progression-free survival in patients with HER2-positive metastatic breast cancer receiving lapatinib monotherapy.
abstract: BACKGROUND
  Changes in serum human epidermal growth factor receptor 2 (HER2) levels associated with clinical outcomes, including objective response rate, progression-free survival (PFS), and overall survival have been reported in patients with metastatic breast cancer (MBC) receiving trastuzumab and chemotherapy. This study investigated whether baseline or changes in serum HER2 correlated with overall response rate (ORR) and/or PFS in patients with MBC receiving first-line lapatinib monotherapy.
  
  
  METHODS
  The EGF20009 study investigated lapatinib monotherapy in 138 HER2-positive patients with MBC previously untreated for their metastatic disease. Serum was collected and assessed at baseline and every 4 weeks for 16 weeks after treatment initiation. Disease assessment was performed at weeks 8 and 12 and every 12 weeks thereafter. A ≥ 20% decrease or increase in serum HER2 was defined as a significant change.
  
  
  RESULTS
  Seventy-nine percent of patients had elevated baseline serum HER2. Baseline serum HER2 was associated with ORR (P = .043) but not PFS. Patients with a ≥ 20% decrease from baseline of serum HER2 at weeks 4, 8, 12, and 16 had a significantly increased ORR and prolonged PFS. Conversely, those with a ≥ 20% increase from baseline had a significantly lower ORR and shorter PFS.
  
  
  CONCLUSIONS
  Significant decreases in serum HER2 levels during the first 16 weeks of lapatinib monotherapy were associated with better clinical outcome (longer PFS and increased ORR) in HER2-positive MBC patients.
authors: Penn State Hershey Cancer Institute, Hematology-Oncology, Penn State/Hershey Medical Center, Hershey, Pennsylvania, USA. alipton@psu.edu
authors: Allan
authors: A
authors: Lipton
authors: Kim
authors: K
authors: Leitzel
authors: Suhail M
authors: SM
authors: Ali
authors: Walter
authors: W
authors: Carney
authors: Greg
authors: G
authors: Platek
authors: Klaudia
authors: K
authors: Steplewski
authors: Ron
authors: R
authors: Westlund
authors: Robert
authors: R
authors: Gagnon
authors: Anne-Marie
authors: AM
authors: Martin
authors: Julie
authors: J
authors: Maltzman
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D000077341:Lapatinib; D009362:Neoplasm Metastasis; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood*; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000077341:Lapatinib; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases