title: Phase 2, multicenter, single-arm study of eribulin mesylate with trastuzumab as first-line therapy for locally recurrent or metastatic HER2-positive breast cancer.
abstract: BACKGROUND
  The aim of this study was to assess efficacy and safety of eribulin with trastuzumab as first-line therapy for locally recurrent or metastatic HER2+ breast cancer.
  
  
  METHODS
  In this multicenter, phase II, single-arm study, patients with recurrent or metastatic HER2+ breast cancer received eribulin mesylate at 1.4 mg/m(2) intravenously (I.V.) on days 1 and 8 of each 21-day cycle with an initial trastuzumab dose of 8 mg/kg I.V. on day 1, followed by 6 mg/kg of trastuzumab on day 1 of each subsequent cycle. Tumor assessments were conducted every 6 weeks for the first 6 cycles and every 12 weeks thereafter. The primary end point was ORR, and secondary end points included PFS, TTR, DOR, and safety.
  
  
  RESULTS
  Fifty-two patients were enrolled. Fifty-one patients (98.1%) had metastatic disease, 25 (48.1%) with liver metastases, 24 (46.2%) with lung metastases, and 19 (36.5%) with bone metastases. Patients received a median of 10.0 cycles of eribulin and 11.0 cycles of trastuzumab. The ORR was 71.2% (n = 37) with median TTR of 1.3 months, DOR of 11.1 months, and PFS of 11.6 months. The most common Grade 3/4 treatment-emergent adverse events were neutropenia in 20 (38.5%) patients, peripheral neuropathy in 14 (26.9%; all Grade 3) patients, fatigue in 4 (7.7%) patients, and febrile neutropenia in 4 (7.7%) patients.
  
  
  CONCLUSIONS
  Because of the high ORR, prolonged median PFS, and acceptable safety profile, combination eribulin/trastuzumab is an acceptable treatment option for locally recurrent or metastatic HER2+ breast cancer.
authors.affiliation: Department of Hematology Oncology, US Oncology-Cancer Care Centers of South Texas, San Antonio, TX.
authors.forename: Sharon
authors.initials: S
authors.lastname: Wilks
authors.affiliation: Department of Medicine, Univerisy of Pittsburgh Medical Center, Pittsburgh, PA.
authors.forename: Shannon
authors.initials: S
authors.lastname: Puhalla
authors.affiliation: Breast Cancer Research, Texas Oncology-Baylor Charles A. Sammons Cancer Center US Oncology, Dallas, TX.
authors.forename: Joyce
authors.initials: J
authors.lastname: O'Shaughnessy
authors.affiliation: Division of Hematology Oncology, West Clinic, Memphis, TN.
authors.forename: Lee
authors.initials: L
authors.lastname: Schwartzberg
authors.affiliation: Medical Affairs, Eisai Inc, Woodcliff Lake, NJ.
authors.forename: Erhan
authors.initials: E
authors.lastname: Berrak
authors.affiliation: Biostatistics, Eisai Inc, Woodcliff Lake, NJ.
authors.forename: James
authors.initials: J
authors.lastname: Song
authors.affiliation: Medical Affairs, Eisai Inc, Woodcliff Lake, NJ.
authors.forename: David
authors.initials: D
authors.lastname: Cox
authors.affiliation: Department of Medicine, Weill Cornell Medical College, New York, NY. Electronic address: ltv2001@med.cornell.edu.
authors.forename: Linda
authors.initials: L
authors.lastname: Vahdat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D018275:Carcinoma, Lobular / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000556:secondary; D005260:Female; D005500:Follow-Up Studies; D005663:Furans / Q000008:administration & dosage; D006801:Humans; D007659:Ketones / Q000008:administration & dosage; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D009367:Neoplasm Staging; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D015996:Survival Rate; D000068878:Trastuzumab; D000095662:Polyether Polyketides
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D005663:Furans; D007659:Ketones; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; C508053:ERBB2 protein, human; C490954:eribulin; D000095662:Polyether Polyketides
keywords: Advanced breast cancer; Breast neoplasm; Chemotherapy; Nontaxane microtubule dynamics inhibitor; Oncology