SWOG S0215: a phase II study of docetaxel and vinorelbine plus filgrastim with weekly trastuzumab for HER2-positive, stage IV breast cancer

Breast Cancer Res Treat. 2011 Nov;130(1):123-31. doi: 10.1007/s10549-011-1698-5. Epub 2011 Aug 9.

Abstract

SWOG trial S0102 showed significant activity of the combination of docetaxel and vinorelbine in HER2-negative metastatic breast cancer (MBC). For HER2-positive patients, additional benefit may occur with the addition of trastuzumab due to its synergy with docetaxel and vinorelbine. Patients with HER2-positive MBC, but without prior chemotherapy for MBC or adjuvant taxane, were eligible. Docetaxel (60 mg/m²) was given intravenously on Day 1, vinorelbine (27.5 mg/m²) intravenously on Days 8 and 15, and filgrastim (5 µg/kg) on Days 2-21 of a 21-day cycle. In addition, patients received weekly infusions of trastuzumab (2 mg/kg) after an initial bolus of 4 mg/kg. The primary outcome was 1 year overall survival (OS), with secondary outcomes of progression-free survival (PFS), response rate, and toxicity. Due to slow accrual (February 2003-December 2006), enrollment was stopped after 76 of 90 planned patients. There have been 32 deaths and 51 progressions among the 74 eligible patients who received treatment. The estimated 1 year OS was 93% (95% CI 84-97%) with a median of 48 months. One-year PFS was 70% (95% CI 58-79%) with a median of 20 months. Response rate for measurable disease was 84%. No deaths were attributed to treatment. Grade 4 toxicities were reported for 19% with neutropenia the most common (15%). The most common grade 3 toxicities (33%) were leucopenia (14%) and fatigue (10%). The combination of trastuzumab, docetaxel, and vinorelbine is effective as first-line chemotherapy in HER2-positive MBC with minimal toxicity. One-year survival estimates are among the highest reported in this population.

Trial registration: ClinicalTrials.gov NCT00041067.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Docetaxel
  • Female
  • Filgrastim
  • Granulocyte Colony-Stimulating Factor / administration & dosage
  • Humans
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasm Staging
  • Receptor, ErbB-2 / metabolism*
  • Recombinant Proteins / administration & dosage
  • Taxoids / administration & dosage
  • Trastuzumab
  • Treatment Outcome
  • Vinblastine / administration & dosage
  • Vinblastine / analogs & derivatives
  • Vinorelbine

Substances

  • Antibodies, Monoclonal, Humanized
  • Recombinant Proteins
  • Taxoids
  • Granulocyte Colony-Stimulating Factor
  • Docetaxel
  • Vinblastine
  • Receptor, ErbB-2
  • Trastuzumab
  • Filgrastim
  • Vinorelbine

Associated data

  • ClinicalTrials.gov/NCT00041067

Grants and funding