Final Results of a Phase II Study of Nab-Paclitaxel, Bevacizumab, and Gemcitabine as First-Line Therapy for Patients With HER2-negative Metastatic Breast Cancer

Breast Cancer Res Treat. 2010 Sep;123(2):427-35. doi: 10.1007/s10549-010-1002-0. Epub 2010 Jun 29.

Abstract

In order to examine the efficacy and safety of nanoparticle albumin-bound paclitaxel (nab-P) in combination with bevacizumab (B) and gemcitabine (G) for the first-line treatment of patients with HER2-negative metastatic breast cancer (MBC). In this single-center, open-label phase II trial, patients with HER2-negative MBC received gemcitabine 1500 mg/m(2), nab-paclitaxel 150 mg/m(2), and bevacizumab 10 mg/kg (each administered intravenously) on days 1 and 15 of a 28-day cycle. The primary end point was progression free survival (PFS); secondary end points were overall response rate (ORR), complete (CR) and partial (PR) response rates, clinical benefit (ORR + stable disease), overall survival (OS), and safety. Thirty patients were enrolled. One patient was ineligible and was not included in analysis. Median PFS was 10.4 months (95% CI: 5.6-15.2 months). ORR was 75.9%, comprising eight (27.6%) CRs and 14 (48.3%) PRs; five patients had stable disease (SD) and two patients (6.9%) had progressive disease (PD) as their best response. The clinical benefit rate was 93.1% (27/29) in the overall group and 84.6% in the triple-negative cohort (11/13). The 18-month survival rate was 77.2% (95% CI: 51.1-90.5%). Eight (27.6%) patients experienced grade 3 or 4 toxicity: grade 4 neutropenic fever (n = 1) and grade 3 infection (n = 6), leukopenia, thrombocytopenia, peripheral neuropathy, seizure, shortness of breath, hematuria, and cardiac tamponade (one each). First-line therapy with nab-P, B, and G demonstrated a median PFS of 10.4 months and a 75.9% ORR with acceptable toxicity; this novel combination warrants investigation in a randomized study.

Publication types

  • Clinical Trial, Phase II
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Antibodies, Monoclonal / administration & dosage
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Bevacizumab
  • Breast Neoplasms / chemistry
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / secondary
  • Breast Neoplasms, Male / chemistry
  • Breast Neoplasms, Male / drug therapy*
  • Breast Neoplasms, Male / mortality
  • Breast Neoplasms, Male / secondary
  • Deoxycytidine / administration & dosage
  • Deoxycytidine / analogs & derivatives
  • Disease-Free Survival
  • Drug Administration Schedule
  • Female
  • Florida
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Paclitaxel / administration & dosage
  • Proportional Hazards Models
  • Receptor, ErbB-2 / analysis*
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Treatment Outcome

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Deoxycytidine
  • Bevacizumab
  • gemcitabine
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel