Background: In CALGB 90206, a phase III trial of IFN +/- Bev, the addition of Bev was associated with an improved progression-free survival (PFS) in RCC pts. Previously, we assessed a panel of soluble cytokines and angiogenic factors and demonstrated that IL-6 and HGF were predictive of overall survival (OS) from Bev. The objective was to evaluate the prognostic importance of tissue expression levels of cytokines and angiogenic factors in pre-treatment specimens from CALGB 90206 pts and to test whether they interacted with the treatment arm in predicting OS and PFS. Methods: Tissue microarrays were constructed using 3 cores from pretreatment specimens from 220 patients and stained for VEGFR1-3, VEGF A, B, C and D, HGF, c-Met, IL-6, IL-6R and STAT3 using a method of quantitative immunofluorescence. Vessel density was quantified by area of CD-34 staining. The proportional hazards model was used to test for the prognostic importance of marker levels (prognostic factors) and whether they interacted with the treatment arm (predictive factors) in predicting OS and PFS using prior nephrectomy and Motzer risk groups as stratification factors. No adjustment for multiplicity was performed. Results: On multivariable analysis, the onlymarker predictive of PFS independent of treatment was HGF, while IL-6 had an interaction with treatment (p-value for interaction = 0.02). None of the markers tested were predictive or prognostic of OS. Conclusions: Expression of HGF in pre-treatment specimens was prognostic for PFS in RCC patients and IL-6 was predictive of PFS in Bev treated patients, consistent with our findings in plasma. If validated, these data suggest that IL-6 may help guide use of anti-VEGF based therapies.

*Based on the interaction term; ** Within arm estimates.