North central cancer treatment group (NCCTG) N0537: phase II trial of VEGF-trap in patients with metastatic breast cancer previously treated with an anthracycline and/or a taxane.

Abstract

INTRODUCTION:

Angiogenesis is an established target for the treatment of MBC. Aflibercept (VEGF-Trap) is a humanized fusion protein, which binds VEGF-A, VEGF-B, and PIGF-1 and -2.

PATIENTS AND METHODS:

A 2-stage phase II study with primary end points of confirmed tumor response and 6-month progression-free survival (PFS). If either end point was promising after the initial 21 patients, an additional 20 patients would be enrolled. Measurable disease, <2 previous chemotherapy treatments, previous anthracycline or taxane therapy, and Eastern Cooperative Oncology Group performance status of 0 or 1 were required. Aflibercept was given at a dose of 4 mg/kg intravenous every 14 days.

RESULTS:

Twenty-one patients were enrolled; 71% had visceral disease, 57% were estrogen receptor negative, 19% had HER2(+) disease with previous trastuzumab treatment, and 33% had 2 previous chemotherapy regimens. Partial response rate was 4.8% (95% confidence interval [CI], 0.1%-23.8%) and 6-month PFS was 9.5% (95% CI, 1.2%-30.4%). Neither primary end point met efficacy goals and the study was terminated. A median of 3 cycles was given. Median PFS was 2.4 months. Common grade 3 or 4 adverse events were hypertension (33%), fatigue (19%), dyspnea (14%), and headache (14%). Two cases of severe left ventricular dysfunction were noted.

CONCLUSIONS:

Aflibercept did not meet efficacy goals in patients previously treated with MBC. Toxicity was as expected for anti-VEGF therapy.

• Authors: Kostandinos Sideras, Amylou C Dueck, Timothy J Hobday, Kendrith M Rowland Jr, Jacob B Allred, Donald W Northfelt, Wilma L Lingle, Robert J Behrens, Tom R Fitch, Daniel A Nikcevich, Edith A Perez
• Journal: Clinical breast cancer (Clin Breast Cancer) Vol. 12 Issue 6 Pg. 387-91 (Dec 2012) ISSN: 1938-0666 [Electronic] United States
• PMID: 23083501 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2012 Elsevier Inc. All rights reserved.

Chemical References

• Anthracyclines
• Antineoplastic Agents
• Bridged-Ring Compounds
• Recombinant Fusion Proteins
• Taxoids
• aflibercept
• taxane
• Receptors, Vascular Endothelial Growth Factor

Topics

• Adenocarcinoma (drug therapy, mortality, pathology)
• Adult
• Aged
• Anthracyclines (administration & dosage)
• Antineoplastic Agents (adverse effects, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Breast Neoplasms (drug therapy, mortality, pathology)
• Bridged-Ring Compounds (administration & dosage)
• Chemotherapy, Adjuvant
• Drug Resistance, Neoplasm (drug effects)
• Female
• Humans
• Medical Oncology (organization & administration)
• Middle Aged
• Neoplasm Metastasis
• Receptors, Vascular Endothelial Growth Factor (adverse effects, therapeutic use)
• Recombinant Fusion Proteins (adverse effects, therapeutic use)
• Societies, Medical
• Survival Analysis
• Taxoids (administration & dosage)
• United States