Lapatinib-plus-pegylated liposomal doxorubicin in advanced HER2-positive breast cancer following trastuzumab: a phase II trial

Anticancer Res. 2015 Jan;35(1):517-21.

Abstract

Background: Trastuzumab, one important treatment option for HER2-positive metastatic breast cancer (MBC) is limited by its cardiotoxic potential. Lapatinib and pegylated liposomal doxorubicin (PLD) represent a cardiosparing alternative that can cross the blood brain barrier. This is important, because one third of breast cancer patients develop brain metastases.

Patients and methods: We included 24 patients with HER2-positive MBC progressing under trastuzumab. They received 1,250 mg lapatinib daily until progression plus PLD (40 mg/m(2)) every 4 weeks for maximal 6 cycles. The primary end-point was the overall response rate (ORR). Secondary end-points were progression-free survival (PFS), overall survival (OS), 1-year PFS and 1-year OS rates.

Results: ORR was 54%. Median PFS was 5.8 and median OS 23.3 months. The one-year PFS rate was 27% and 1-year OS rate 76%.

Conclusion: Lapatinib-plus-PLD is active and safe in HER2-positive MBC, especially suitable for patients with cardiological risk or brain metastases.

Keywords: Her2-positive; Metastatic breast cancer; lapatinib; pegylated liposomal doxorubicin.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Antibodies, Monoclonal, Humanized / administration & dosage
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Brain Neoplasms / drug therapy*
  • Brain Neoplasms / metabolism
  • Brain Neoplasms / mortality
  • Brain Neoplasms / secondary
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Doxorubicin / administration & dosage
  • Doxorubicin / analogs & derivatives
  • Drug Resistance, Neoplasm
  • Female
  • Humans
  • Kaplan-Meier Estimate
  • Lapatinib
  • Middle Aged
  • Polyethylene Glycols / administration & dosage
  • Quinazolines / administration & dosage
  • Receptor, ErbB-2 / metabolism*
  • Trastuzumab
  • Treatment Outcome

Substances

  • Antibodies, Monoclonal, Humanized
  • Quinazolines
  • liposomal doxorubicin
  • Lapatinib
  • Polyethylene Glycols
  • Doxorubicin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab