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Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.


ABSTRACT: 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.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.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).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.

SUBMITTER: Bates DO 

PROVIDER: S-EPMC3602975 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Association between VEGF splice isoforms and progression-free survival in metastatic colorectal cancer patients treated with bevacizumab.

Bates David O DO   Catalano Paul J PJ   Symonds Kirsty E KE   Varey Alex H R AH   Ramani Pramila P   O'Dwyer Peter J PJ   Giantonio Bruce J BJ   Meropol Neal J NJ   Benson Al Bowen AB   Harper Steven J SJ  

Clinical cancer research : an official journal of the American Association for Cancer Research 20121025 22


<h4>Purpose</h4>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.<h4>Experimental design</h4>Blinded tumor samples from the phase III trial of FOLFOX4 ± bevacizum  ...[more]

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