Abstract
Background: We investigated plasma levels of circulating angiogenic factors (CAFs) involved in angiogenesis in patients (pts) with mRCC treated with first-line pazopanib to assess potential biomarkers of clinical outcome. Patients and Methods: Pts (n = 25) with mRCC receiving first-line pazopanib at Istituto Nazionale Tumori of Milan between July 2015 and February 2017 were prospectively enrolled in the study. Plasma samples were obtained at different time-points: before treatment and every 4 weeks until radiographic disease progression (PD) as per RECIST 1.1. assessed by CT scan every 12 weeks. Levels of 7 CAFs of interest including: IL-6, IL-8, SDF-1, VEGF-A, HGF, Osteopontin and E-selectin were quantified by Luminex® technology. Baseline levels and changes during treatment were analyzed for association with efficacy (progression-free survival [PFS] and objective response). Results: 21 out of 25 pts enrolled were evaluated. The median follow up was 8 months (IQR 5.1 months). Overall plasma levels of SDF-1 (p<.0001), VEGF-A (p=.0052) and IL-8 (p=.0275) showed the highest modulation during treatment. At the end of first pazopanib cycle (week 4) plasma VEGF-A levels were significantly higher in pts with partial response (PR) than in pts with PD. IL-8 levels were significantly higher in pts with PD vs pts with PR at the time of response (p=.0481). Moreover baseline IL-8 levels were significantly higher in pts with PD vs pts with stable disease (SD) (p=.0181). Mean levels of SDF-1 (p=.0022), HGF (p=.0002), osteopontin (p<.0001) and E-selectin (p<.0001) were significantly associated with best response (PR vs SD vs PD) while IL-6 levels were significantly associated with PFS (p=.0082). The 6 months and one year estimated PFS rate was 73% and 63% respectively. Conclusions: Treatment with first-line pazopanib is associated with variation of CAFs levels. Week 4 levels of VEGF-A as well as pretreatment levels of IL-8 showed the strongest correlation with PD suggesting that monitoring these CAFs during treatment may be useful for identifying patients likely to respond. These findings warrant further investigation in larger trials.
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