A phase II study of lapatinib and bevacizumab as treatment for HER2-overexpressing metastatic breast cancer

Hope S. Rugo, A. Jo Chien, Sandra X. Franco, Alison T. Stopeck, Alexa Glencer, Soumi Lahiri, Michael C. Arbushites, Janet Scott, John W. Park, Clifford Hudis, Ben Nulsen, Maura N. Dickler

Research output: Contribution to journalReview articlepeer-review

35 Scopus citations

Abstract

Preclinical data have demonstrated that the combination of antihuman epidermal growth factor receptor-2 (anti-HER2) and antivascular endothelial growth factor (anti-VEGF)-targeted agents has antitumor activity; these data indicate certain patients with HER2-overexpressing breast cancer may derive clinical benefit from this combination. The purpose of this single-arm phase II study was to determine the efficacy and safety of the dual-targeting combination of lapatinib and bevacizumab. Women with HER2-overexpressing advanced breast cancer received 1,500 mg oral lapatinib daily plus 10 mg/kg IV bevacizumab every 2 weeks. The primary endpoint was progression-free survival (PFS) at week 12; secondary endpoints included overall tumor response rate (ORR), clinical benefit rate (CBR), duration of response, time-to-response, PFS, and safety. Circulating tumor cells (CTC) and circulating endothelial cells (CEC) were measured at baseline and during study treatment as potential response markers. Fifty-two patients with stage IV disease were enrolled. The 12-week investigator-assessed PFS rate was 69.2% (95% confidence interval [CI]: 54.9, 81.3). Median PFS was 24.7 weeks (95% CI: 20.4, 35.1), and the CBR was 30.8% (95% CI: 18.7, 45.1). Of 45 patients with measurable disease, 6 were determined to have a partial response per Response Evaluation Criteria in Solid Tumors (ORR: 13.3%; 95% CI: 5.1, 26.8). The most common adverse events (AEs) included diarrhea, rash, and fatigue; most of these were either grade 1 or 2. Clinical responses were correlated with decreases in CTC and CEC. Lapatinib plus bevacizumab was active in patients with HER2-overexpressing breast cancer. The AE profile of the combination was consistent with the known profiles for these agents.

Original languageEnglish (US)
Pages (from-to)13-20
Number of pages8
JournalBreast Cancer Research and Treatment
Volume134
Issue number1
DOIs
StatePublished - Jul 2012

Keywords

  • Bevacizumab
  • Breast cancer
  • HER2
  • Lapatinib
  • Targeted therapy
  • Tyrosine kinase inhibitor
  • VEGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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