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 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).
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.
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.
Clinical cancer research : an official journal of the American Association for Cancer Research. 2020 Aug 18 [Epub ahead of print]
Jean-Francois Martini, Elizabeth R Plimack, Toni K Choueiri, David F McDermott, Igor Puzanov, Mayer N Fishman, Daniel C Cho, Ulka Vaishampayan, Brad Rosbrook, Kathrine C Fernandez, Jamal C Tarazi, Saby George, Michael B Atkins
Translational Oncology, Pfizer Inc., Hematology and Oncology, Fox Chase Cancer Center ., Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School., Heme/Onc, Beth Israel Deaconess Medical Center, Harvard Medical School., Medicine, Roswell Park Comprehensive Cancer Center., Moffitt Cancer Center., Hematology and Oncology, Perlmutter Cancer Center at NYU Langone Medical Center., Department of Oncology, Karmanos Cancer Institute., Pfizer Oncology, Pfizer Oncology., Medicine, Roswell Park Cancer Institute., Lombardi Comprehensive Cancer Center, Georgetown University Medical Center.