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Tang PA , Cohen SJ , Kollmannsberger C , Bjarnason G , Virik K , MacKenzie MJ , Lourenco L , Wang L , Chen A , Moore MJ
Phase II Clinical and Pharmacokinetic Study of Aflibercept in Patients with Previously Treated Metastatic Colorectal Cancer
Clinical Cancer Research. 2012 Nov;18(21) :6023-6031
AbstractPurpose: 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 naive (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-naive 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-naive 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. Clin Cancer Res; 18(21); 6023-31. (C) 2012 AACR.
NotesTang, Patricia A. Cohen, Steven J. Kollmannsberger, Christian Bjarnason, Georg Virik, Kiran MacKenzie, Mary J. Lourenco, Lillian Wang, Lisa Chen, Alice Moore, Malcolm J. American Society of Clinical Oncology Young Investigator Award; National Cancer Institute [N01-CM-62203] The authors thank Dr. Eric Chen who conducted the pharmacokinetic analysis for this project. Dr. Tang was supported in part by an American Society of Clinical Oncology Young Investigator Award.This work was supported by National Cancer Institute contract number N01-CM-62203. 39 Amer assoc cancer research Philadelphia 049yv