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Martini JF , Plimack ER , Choueiri TK , McDermott DF , Puzanov I , Fishman MN , Cho DC , Vaishampayan U , Rosbrook B , Fernandez KC , Tarazi JC , George S , Atkins MB
Angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment in patients with advanced renal cell carcinoma
Clin Cancer Res. 2020 Nov;26(21) :5598-5608
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PURPOSE: 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. EXPERIMENTAL DESIGN: 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 every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, and 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). RESULTS: Higher baseline tumor levels of CD8 showed a trend toward longer PFS (hazard ratio [HR] 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL-6 was not detected at baseline had longer PFS vs patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS. CONCLUSIONS: 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. ClinicalTrials.gov identifier: NCT02133742.
Martini, Jean-Francois Orcid: 0000-0001-8570-1401 Plimack, Elizabeth R Choueiri, Toni K McDermott, David F Puzanov, Igor Fishman, Mayer N Cho, Daniel C Vaishampayan, Ulka Rosbrook, Brad Fernandez, Kathrine C Tarazi, Jamal C Orcid: 0000-0002-5452-2061 George, Saby Orcid: 0000-0002-0444-5870 Atkins, Michael B Journal Article United States Clin Cancer Res. 2020 Aug 18:clincanres.1408.2020. doi: 10.1158/1078-0432.CCR-20-1408.