Pilot neoadjuvant trial in HER2 positive breast cancer with combination of nab-paclitaxel and lapatinib

Breast Cancer Res Treat. 2012 Apr;132(3):833-42. doi: 10.1007/s10549-011-1411-8. Epub 2011 Feb 27.

Abstract

Lapatinib, a dual kinase inhibitor against epidermal growth factor receptor (EGFR) and human epidermal receptor two (HER2) has shown efficacy in treating HER2 positive breast cancer. Nanoparticle albumin bound (nab) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy. Thirty patients with stage I-III HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000 mg/day and nab-paclitaxel 260 mg/m(2) every 3 weeks for four cycles. The primary end point of the trial was clinical response rate (cRR) with secondary end points including pathologic complete response rate (pCR), tolerability of the combination, and marker response. The cRR was 82.8% (24 patients) with six (20.7%) patients having complete clinical response, 18 (62.1%) having partial clinical response, and five (17.2%) stable disease. A pCR was observed in five of the 28 patients (17.9%). The most frequent grade 2 toxicities were neuropathy in nine patients (30%), fatigue in seven patients (23.3%), rash in 11 patients (36.7%), and bone pain in 10 patients (33.3%). There was no significant drop in the left ventricular ejection fraction (LVEF). Of the tissue markers examined, we were not able to find a predictor of response. The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer. This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer.

Trial registration: ClinicalTrials.gov NCT00331630.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Albumins / administration & dosage
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Biomarkers, Tumor / metabolism*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Carcinoma, Ductal, Breast / drug therapy*
  • Carcinoma, Ductal, Breast / metabolism
  • Carcinoma, Ductal, Breast / mortality
  • Diarrhea / chemically induced
  • Female
  • Heart Function Tests
  • Humans
  • Kaplan-Meier Estimate
  • Lapatinib
  • Middle Aged
  • Neoadjuvant Therapy*
  • Paclitaxel / administration & dosage
  • Pilot Projects
  • Quinazolines / administration & dosage
  • Receptor, ErbB-2 / metabolism*
  • Treatment Outcome

Substances

  • 130-nm albumin-bound paclitaxel
  • Albumins
  • Biomarkers, Tumor
  • Quinazolines
  • Lapatinib
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Paclitaxel

Associated data

  • ClinicalTrials.gov/NCT00331630