title: A phase II study of ixabepilone and trastuzumab for metastatic HER2-positive breast cancer.
abstract: BACKGROUND
  A multicenter NCI-sponsored phase II study was conducted to analyze the safety and efficacy of the combination of ixabepilone with trastuzumab in patients with metastatic HER2-positive breast cancer.
  
  
  METHODS
  Two cohorts were enrolled: cohort 1 had received no prior chemotherapy or trastuzumab for metastatic disease and cohort 2 had received 1-2 prior trastuzumab-containing regimens for metastatic disease. Patients in both cohorts received ixabepilone 40 mg/m(2) as a 3-h infusion and trastuzumab on day 1 of a 21-day cycle. Tumor biomarkers that may predict response to trastuzumab were explored.
  
  
  RESULTS
  Thirty-nine women entered the study with 15 patients in cohort 1 and 24 patients in cohort 2. Across both cohorts, the overall RR was 44%, with a clinical benefit rate (CR + PR + SD for at least 24 weeks) of 56%. Treatment-related toxic effects included neuropathy (grade ≥2, 56%), leukopenia (grade ≥2, 26%), myalgias (grade ≥2, 21%), neutropenia (grade ≥2, 23%), and anemia (grade ≥2, 18%).
  
  
  CONCLUSIONS
  This represents the first study of the combination of ixabepilone with trastuzumab for the treatment of metastatic HER2-positive breast cancer. These results suggest that the combination has encouraging activity as first and subsequent line therapy for metastatic breast cancer.
authors.affiliation: Departments of Medical Oncology. Electronic address: stolaney@partner.org.
authors.forename: S M
authors.initials: SM
authors.lastname: Tolaney
authors.affiliation: Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston.
authors.forename: J
authors.initials: J
authors.lastname: Najita
authors.affiliation: Departments of Research and Development.
authors.forename: J
authors.initials: J
authors.lastname: Sperinde
authors.affiliation: Clinical Research, Monogram Biosciences, Inc., South San Francisco.
authors.forename: W
authors.initials: W
authors.lastname: Huang
authors.affiliation: Departments of Medical Oncology; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston.
authors.forename: W Y
authors.initials: WY
authors.lastname: Chen
authors.affiliation: Departments of Medical Oncology.
authors.forename: J
authors.initials: J
authors.lastname: Savoie
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA.
authors.forename: M
authors.initials: M
authors.lastname: Fornier
authors.affiliation: Departments of Medical Oncology.
authors.forename: E P
authors.initials: EP
authors.lastname: Winer
authors.affiliation: Departments of Medical Oncology.
authors.forename: C
authors.initials: C
authors.lastname: Bunnell
authors.affiliation: Departments of Medical Oncology.
authors.forename: I E
authors.initials: IE
authors.lastname: Krop
mesh_terms: D000328:Adult; D000368:Aged; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D034261:Epothilones / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009362:Neoplasm Metastasis; D000068878:Trastuzumab; D016896:Treatment Outcome
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D034261:Epothilones; C430592:ixabepilone; D000068878:Trastuzumab
keywords: HER2; breast; cancer; ixabepilone; trastuzumab
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