Phase II clinical and pharmacokinetic study of aflibercept in patients with previously treated metastatic colorectal cancer.

Abstract

PURPOSE:

Aflibercept is a recombinant fusion protein of the VEGF receptor (VEGFR) 1 and VEGFR2 extracellular domains. We assessed the safety and efficacy of aflibercept in patients with metastatic colorectal cancer (MCRC) who had received at least one prior palliative regimen.

EXPERIMENTAL DESIGN:

Seventy-five patients were enrolled onto this two-stage phase II trial in two cohorts, bevacizumab naïve (n = 24) and prior bevacizumab (n = 51). Aflibercept was administered at 4 mg/kg i.v. in two-week cycles. The primary endpoint was a combination of objective response rate and 16-week progression-free survival (PFS).

RESULTS:

In the bevacizumab-naïve cohort (n = 24), the best response was stable disease for 16 weeks or more in five of 24 patients. In the prior bevacizumab cohort (n = 50), one patient achieved a partial response and six patients had stable disease for 16 weeks or more. The median PFS in the bevacizumab-naïve and prior bevacizumab cohorts was two months [95% confidence interval (CI): 1.7-8.6 months] and 2.4 months (95% CI: 1.9-3.7 months), respectively. Median overall survival (OS) was 10.4 months (95% CI: 7.6-15.5) and 8.5 months (95% CI: 6.2-10.6), respectively. The most common grade 3 or higher treatment-related adverse events were hypertension, proteinuria, fatigue, and headache. Ten patients discontinued study treatment due to toxicity. Mean free to VEGF-bound aflibercept ratio was 1.82, suggesting that free aflibercept was present in sufficient amount to bind endogenous VEGF.

CONCLUSION:

Aflibercept showed limited single-agent activity in patients with pretreated MCRC with moderate toxicity. Further study of aflibercept with chemotherapy is ongoing.

• Authors: Patricia A Tang, Steven J Cohen, Christian Kollmannsberger, Georg Bjarnason, Kiran Virik, Mary J MacKenzie, Lillian Lourenco, Lisa Wang, Alice Chen, Malcolm J Moore
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 18 Issue 21 Pg. 6023-31 (Nov 01 2012) ISSN: 1557-3265 [Electronic] United States
• PMID: 22977191 (Publication Type: Clinical Trial, Phase II, Journal Article, Multicenter Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
• Copyright: ©2012 AACR.

Chemical References

• Antineoplastic Agents
• Recombinant Fusion Proteins
• aflibercept
• Receptors, Vascular Endothelial Growth Factor

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (adverse effects, pharmacokinetics, therapeutic use)
• Colorectal Neoplasms (drug therapy, mortality, pathology)
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Metastasis
• Prognosis
• Receptors, Vascular Endothelial Growth Factor (adverse effects, pharmacokinetics, therapeutic use)
• Recombinant Fusion Proteins (adverse effects, pharmacokinetics, therapeutic use)
• Treatment Outcome