Dual HER2 inhibition in combination with anti-VEGF treatment is active in heavily pretreated HER2-positive breast cancer

G. S. Falchook, S. L. Moulder, J. J. Wheler, Y. Jiang, C. C. Bastida, R. Kurzrock

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

Background: Preclinical data indicate that dual HER2 inhibition overcomes trastuzumab resistance and that use of an HER2 inhibitor with an anti-angiogenic agent may augment responses. Patients and methods: We conducted a dose-escalation, phase I study of a combination of trastuzumab, lapatinib and bevacizumab. The subset of patients with metastatic breast cancer was analyzed for safety and response. Results: Twenty-six patients with metastatic breast cancer (median = 7 prior systemic therapies) (all with prior trastuzumab; 23 with prior lapatinib; one with prior bevacizumab) received treatment on a range of dose levels. The most common treatment-related grade 2 or higher toxicities were diarrhea (n = 11, 42%) and skin rash (n = 2, 8%). The recommended phase 2 dose was determined to be the full Food and Drug Administration (FDA) approved doses for all the three agents (trastuzumab 8 mg/kg loading dose, 6 mg/kg maintenance dose, intravenously every 3 weeks; lapatinib 1250 mg daily, bevacizumab 15 mg/kg intravenously every 3 weeks). The overall rate of stable disease (SD) ≥6 months and partial or complete remission (PR/CR) was 50% (five patients with SD ≥6 months; seven PRs (including one unconfirmed); one CR). The rate of SD ≥6 months/PR/CR was not compromised in patients who had previously received study drugs, those with brain metastases, and patients treated at lower dose levels. Conclusions: The combination of trastuzumab, lapatinib and bevacizumab was well-tolerated at maximally approved doses of each drug, and its activity in heavily pretreated patients with metastatic breast cancer suggests that it warrants further investigation. ClinTrials.gov ID: NCT00543504.

Original languageEnglish (US)
Pages (from-to)3004-3011
Number of pages8
JournalAnnals of Oncology
Volume24
Issue number12
DOIs
StatePublished - Dec 2013

Keywords

  • Bevacizumab
  • Breast cancer
  • Her2
  • Lapatinib
  • Trastuzumab

ASJC Scopus subject areas

  • Hematology
  • Oncology

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