Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.
| Autor: | Bates DO; Microvascular Research Laboratories, Department of Physiology and Pharmacology, University of Bristol, Bristol, United Kingdom. Dave.Bates@bristol.ac.uk, Catalano PJ, Symonds KE, Varey AH, Ramani P, O'Dwyer PJ, Giantonio BJ, Meropol NJ, Benson AB, Harper SJ |
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| Jazyk: | angličtina |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2012 Nov 15; Vol. 18 (22), pp. 6384-91. Date of Electronic Publication: 2012 Oct 25. |
| DOI: | 10.1158/1078-0432.CCR-12-2223 |
| Abstrakt: | Purpose: Bevacizumab improves survival for patients with metastatic colorectal cancer with chemotherapy, but no proven predictive markers exist. The VEGF-A splice form, VEGF(165)b, anti-angiogenic in animal models, binds bevacizumab. We tested the hypothesis that prolonged progression-free survival (PFS) would occur only in patients with low relative VEGF(165)b levels treated with bevacizumab. Experimental Design: Blinded tumor samples from the phase III trial of FOLFOX4 ± bevacizumab were assessed for VEGF(165)b and VEGF(total) by immunohistochemistry and scored relative to normal tissue. A predictive index (PI) was derived from the ratio of VEGF(165)b:VEGF(total) for 44 samples from patients treated with FOLFOX + bevacizumab (arm A) and 53 samples from patients treated with FOLFOX4 (arm B), and PFS, and overall survival (OS) analyzed on the basis of PI relative to median ratio. Results: Unadjusted analysis of PFS showed significantly better outcome for individuals with VEGF(165)b:VEGF(total) ratio scores below median treated with FOLFOX4 + bevacizumab compared with FOLFOX4 alone (median, 8.0 vs. 5.2 months; P < 0.02), but no effect of bevacizumab on PFS in patients with VEGF(165)b:VEGF(total) ratio >median (5.9 vs. 6.3 months). These findings held after adjustment for other clinical and demographic features. OS was increased in arm A (median, 13.6 months) compared with arm B (10.6 months) in the low VEGF(165)b group, but this did not reach statistical significance. There was no difference in the high VEGF(165)b:VEGF(total) group between FOLFOX + bevacizumab (10.8 months) and FOLFOX alone (11.3 months). Conclusion: Low VEGF(165)b:VEGF(total) ratio may be a predictive marker for bevacizumab in metastatic colorectal cancer, and individuals with high relative levels may not benefit. (©2012 AACR.) |
| Databáze: | MEDLINE |
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