Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma.

Abstract

Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment. Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS). Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; <i>P</i> = 0.091). Higher baseline serum levels of CXCL10 (<i>P</i> = 0.0197) and CEACAM1 (<i>P</i> = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; <i>P</i> = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes <i>CA9</i> (<i>P</i> = 0.084), <i>HIF1A</i> (<i>P</i> = 0.064), and <i>IFNG</i> (<i>P</i> = 0.073) showed trending associations with ORR, and <i>AKT3</i> (<i>P</i> = 0.0145), <i>DDX58</i> (<i>P</i> = 0.0726), <i>GZMA</i> (<i>P</i> = 0.0666), <i>LCN2</i> (<i>NGAL</i>; <i>P</i> = 0.0267), and <i>PTPN11</i> (<i>P</i> = 0.0287) with PFS. With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.