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

• Published in: Clinical cancer research 2020-11, Vol.26 (21), p.5598-5608
• Main Authors: Martini, Jean-François, Plimack, Elizabeth R, Choueiri, Toni K, McDermott, David F, Puzanov, Igor, Fishman, Mayer N, Cho, Daniel C, Vaishampayan, Ulka, Rosbrook, Bradley, Fernandez, Kathrine C, Tarazi, Jamal C, George, Saby, Atkins, Michael B
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - administration & dosage; Antibodies, Monoclonal, Humanized - adverse effects; Antigens, Neoplasm - blood; Axitinib - administration & dosage; Axitinib - adverse effects; Biomarkers, Tumor - blood; Biomarkers, Tumor - genetics; Carbonic Anhydrase IX - blood; Carcinoma, Renal Cell - blood; Carcinoma, Renal Cell - drug therapy; Carcinoma, Renal Cell - genetics; Carcinoma, Renal Cell - pathology; DEAD Box Protein 58 - blood; Dose-Response Relationship, Drug; Female; Granzymes - blood; Humans; Hypoxia-Inducible Factor 1, alpha Subunit - blood; Interferon-gamma - blood; Lipocalin-2 - blood; Male; Middle Aged; Neoplasm Staging; Neovascularization, Pathologic - blood; Neovascularization, Pathologic - drug therapy; Neovascularization, Pathologic - genetics; Neovascularization, Pathologic - pathology; Progression-Free Survival; Protein Tyrosine Phosphatase, Non-Receptor Type 11 - blood; Receptors, Immunologic - blood; Treatment Outcome
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-20-1408

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; = 0.091). Higher baseline serum levels of CXCL10 ( = 0.0197) and CEACAM1 ( = 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; = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes ( = 0.084), ( = 0.064), and ( = 0.073) showed trending associations with ORR, and ( = 0.0145), ( = 0.0726), ( = 0.0666), ( ; = 0.0267), and ( = 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.