VEGF levels may predict survival in renal cell carcinoma patients

Chicago-In patients with metastatic renal cell carcinoma, baseline levels of vascular endothelial growth factor (VEGF) predicted overall and progression-free survival, providing additional support for therapies that target VEGF, a French oncologist reported at the American Society of Clinical Oncology annual meeting here.

A two-fold increase in median baseline VEGF correlated with a 39% increase in mortality risk, said Sylvie Negrier, MD, PhD, professor of oncology at Centre Leon-Berard in Lyon. A doubling of the baseline VEGF value was associated with a 20% increased likelihood of disease progression.

"Conversely to previous results obtained in a non-selected population, serum IL-6 is not confirmed as an independent prognostic factor in this cohort that excludes patients with poor outcome," Dr. Negrier said. "Serum VEGF level appears to be an independent prognostic factor for event-free survival, as well as for overall survival in patients with good or intermediate prognosis. This result argues in favor of newly available treatments that target VEGF or its receptors."

Investigators obtained pre-treatment serum samples from 302 patients with metastatic RCC enrolled in two parallel, randomized clinical trials of cytokine therapy. The study group comprised 74 patients with good prognosis and 228 with intermediate prognosis by criteria used in the cytokine trials. Poor-prognosis patients were excluded from the analysis.

Baseline serum cytokine values were 7.34 pg/mL for IL-6, 0.51 ng/mL for M-CSF, 405.5 pg/mL for VEGF, and 0 (mean of 165.70 ng/mL) for MIP-3.

Median overall survival for the entire cohort was approximately 21 months. The survival data were stratified according to quartiles of baseline cytokine values. For IL-6, a baseline value of <35 pg/mL correlated with significantly better overall survival compared with patients who had higher baseline levels (p≤.0001). For VEGF, a baseline serum level of <755 pg/mL predicted improved survival compared with patients who had higher baseline levels (p<.0001).

In univariate analysis, baseline M-CSF levels <0.37 ng/mL also predicted improved survival (p=.0003). The analysis revealed no prognostic value for baseline MIP-3 levels.

Similar results emerged from an analysis of event-free survival by baseline cytokine levels, as only the levels of IL-6 (p=.0021) and VEGF (p=.0019) had prognostic value. Median event-free survival for all 302 patients was 4 months.

In multivariate analysis, only VEGF remained an independent predictor of survival. The finding held up regardless of whether cytokine levels were analyzed as a continuous variable or according to threshold values.