P0201 Circulating biomarkers and outcomes in a phase 2 trial of first-line everolimus alternating with sunitinib for advanced renal cell carcinoma (ANZUP 0901—the EVERSUN Trial)

Background We investigated whether changes in biomarker levels correlated with clinical outcomes of progression-free survival (PFS), overall survival (OS), objective tumour response (OTR), and toxicity (cycle 1, grade 3–5 adverse events), in patients receiving alternating everolimus and sunitinib for advanced renal cell cancer. Methods Blood was drawn at nine timepoints: cycle 1 days 1, 15, and 29 (start, middle, and end of sunitinib treatment), cycle 1 days 43, 57, and 71 (start, middle, and end of everolimus treatment), cycle 2 day 1, and cycle 3 day 1, and at the end of treatment. Blood was tested by multiplex immunoassays (Bio-Plex, BioRad) or ELISA (R & D Systems DuoSets) for protein biomarkers bFGF, CAIX, E-selectin, HIF1, IL8, NGAL, PDGF, PLGF, VCAM, VEGF-A, C, and D, and VEGFR1–3. Biomarker changes from baseline were dichotomised according to median change score. Prognostic value of change levels from baseline to day 29 and day 71 were evaluated univariately using Cox proportional hazard regression for PFS and OS; logistic regression was applied to OTR and toxicity. Findings Of 55 patients assessed, mean age was 61 years, 71% were male, 16% were Memorial Sloan-Kettering Cancer Center (MSKCC) favourable risk, and 84% were intermediate risk. There were 47 progression events and 30 deaths after a median follow-up of 20 months. Biomarker level profiles over time reflected the expected pharmacodynamic effects of sunitinib and everolimus treatment. Longer PFS was associated with a large increase in IL8 level at day 29 (hazard ratio [HR] 0.5, p  = 0.05) and a large increase in VEGFR3 level at day 71 (HR 0.5, p  = 0.04); longer OS was associated with a small decrease in VEGFR3 at day 29 (HR 0.4, p  = 0.02). Toxicity was associated with a small decrease in VEGF-C at day 71 (odds ratio 6.2, p  = 0.01). These associations were not statistically significant after adjustment for multiple comparisons. Interpretation This exploratory study did not find strong associations between clinical outcomes and changes from baseline in circulating biomarkers.