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

Angiogenesis is an established target in metastatic breast cancer (MBC). Aflibercept (vascular endothelial growth factor [VEGF]-trap) is a humanized fusion protein which binds VEGF-A, VEGF-B, and placental growth factors PIGF-1, and PIGF-2. A phase II study was conducted to test the safety and efficacy of aflibercept in patients with MBC. Though safety was acceptable, aflibercept did not demonstrate sufficient activity to warrant further study, as a single agent, in this patient population. 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. Clinical Breast Cancer, Vol. 12, No. 6, 387-91 (c) 2012 Elsevier Inc. All rights reserved.