Circulating VEGF and eNOS variations as predictors of outcome in metastatic colorectal cancer patients receiving bevacizumab.
Level 2 - randomized trial
Biomarker substudy nested within a randomized controlled trial
PubMed 28465540 · doi:10.1038/s41598-017-01420-0
What was done
Researchers measured circulating mRNA levels of five biomarkers (VEGF-A, eNOS, EPHB4, COX2, and HIF-1α) using qRT-PCR on peripheral blood taken at baseline, first clinical evaluation, and disease progression. Blood was analyzed from 129 patients with metastatic colorectal cancer enrolled in the prospective multicenter ITACa trial, where patients were randomized to FOLFOX4/FOLFIRI chemotherapy alone (n = 65) or with bevacizumab (n = 64). Biomarker levels and longitudinal changes were evaluated for associations with objective response, progression-free survival, and overall survival (OS).
What was found
VEGF and eNOS expression levels were significantly correlated in both treatment groups (Spearman's r = 0.80, P < 0.0001; and r = 0.75, P < 0.0001, respectively). Among bevacizumab-treated patients, those with a greater than 30% reduction in both eNOS and VEGF levels from baseline to the first clinical evaluation had significantly longer overall survival than those without such a reduction (median OS 31.6 months, 95% CI 21.3–49.5 vs. 14.4 months, 95% CI 9.0–22.7; HR 0.38, 95% CI 0.19–0.78, P = 0.008). No numerical outcome data were reported in the abstract for EPHB4, COX2, HIF-1α, or progression-free survival.
Why it matters
Dynamic decreases in circulating VEGF and eNOS mRNA early in therapy may serve as noninvasive predictive biomarkers to identify metastatic colorectal cancer patients who derive survival benefit from bevacizumab.
Limits
The sample size for biomarker analysis was small (64 patients receiving bevacizumab). The abstract does not indicate whether the >30% biomarker reduction threshold was pre-specified or post-hoc, omits numerical results for the other three evaluated markers, does not provide comparative survival data based on biomarker modulation in the chemotherapy-only control arm, and lacks external validation.
Cited by
- partial Cancer presence can lead to elevated circulating VEGF levels in blood tests, which can be measured to monitor tumor progression or active metastasis.