title: Trastuzumab and vinorelbine as first-line therapy for HER2-overexpressing metastatic breast cancer: multicenter phase II trial with clinical outcomes, analysis of serum tumor markers as predictive factors, and cardiac surveillance algorithm.
abstract: OBJECTIVE
  Trastuzumab-based therapy improves survival for women with human epidermal growth factor receptor 2 (HER2)-positive advanced breast cancer. We conducted a multicenter phase II study to evaluate the efficacy and safety of trastuzumab combined with vinorelbine, and to assess cardiac surveillance algorithms and tumor markers as prognostic tools.
  
  
  METHODS
  Patients with HER2-positive (immunohistochemistry [IHC] 3+-positive or fluorescence in situ hybridization [FISH]-positive) metastatic breast cancer received first-line chemotherapy with trastuzumab and vinorelbine to determine response rate. Eligibility criteria were measurable disease and baseline ejection fraction >or= 50%. Serial testing for HER2 extracellular domain (ECD) was performed.
  
  
  RESULTS
  Fifty-four women from 17 participating centers were entered onto the study. The overall response rate was 68% (95% confidence interval, 54% to 80%). Response rates were not affected by method of HER2 status determination (FISH v IHC) or by prior adjuvant chemotherapy. Median time to treatment failure was 5.6 months; 38% of patients were progression free after 1 year. Concurrent therapy was quite feasible with maintained dose-intensity. Patients received both chemotherapy and trastuzumab on 90% of scheduled treatment dates. Two patients experienced cardiotoxicity in excess of grade 1; one patient experienced symptomatic heart failure. A surveillance algorithm of screening left ventricular ejection fraction (LVEF) at 16 weeks successfully identified women at risk for experiencing cardiotoxicity. Other acute and chronic side effects were tolerable. Lack of decline in HER2 ECD during cycle 1 predicted tumor progression.
  
  
  CONCLUSIONS
  Trastuzumab and vinorelbine constitute effective and well-tolerated first-line treatment for HER2-positive metastatic breast cancer. Patients with normal LVEF can be observed with surveillance of LVEF at 16 weeks to identify those at risk for cardiotoxicity.
authors.affiliation: Dana-Farber Cancer Institute, Brigham & Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. hburstein@partners.org.
authors.forename: Harold J
authors.initials: HJ
authors.lastname: Burstein
authors.forename: Lyndsay N
authors.initials: LN
authors.lastname: Harris
authors.forename: P Kelly
authors.initials: PK
authors.lastname: Marcom
authors.forename: Rosemary
authors.initials: R
authors.lastname: Lambert-Falls
authors.forename: Kathleen
authors.initials: K
authors.lastname: Havlin
authors.forename: Beth
authors.initials: B
authors.lastname: Overmoyer
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Friedlander
authors.forename: Janet
authors.initials: J
authors.lastname: Gargiulo
authors.forename: Rochelle
authors.initials: R
authors.lastname: Strenger
authors.forename: Charles L
authors.initials: CL
authors.lastname: Vogel
authors.forename: Paula D
authors.initials: PD
authors.lastname: Ryan
authors.forename: Mathew J
authors.initials: MJ
authors.lastname: Ellis
authors.forename: Raquel A
authors.initials: RA
authors.lastname: Nunes
authors.forename: Craig A
authors.initials: CA
authors.lastname: Bunnell
authors.forename: Susana M
authors.initials: SM
authors.lastname: Campos
authors.forename: Michele
authors.initials: M
authors.lastname: Hallor
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gelman
authors.forename: Eric P
authors.initials: EP
authors.lastname: Winer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000009:adverse effects; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000097:blood; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018450:Disease Progression; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D011237:Predictive Value of Tests; D012372:ROC Curve; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D016019:Survival Analysis; D000068878:Trastuzumab; D016896:Treatment Outcome; D014747:Vinblastine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D000077235:Vinorelbine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D014747:Vinblastine; D000077235:Vinorelbine