RT Journal Article
SR Electronic
T1 Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma
JF Clinical Cancer Research
JO Clin Cancer Res
FD American Association for Cancer Research
SP 5598
OP 5608
DO 10.1158/1078-0432.CCR-20-1408
VO 26
IS 21
A1 Martini, Jean-François
A1 Plimack, Elizabeth R.
A1 Choueiri, Toni K.
A1 McDermott, David F.
A1 Puzanov, Igor
A1 Fishman, Mayer N.
A1 Cho, Daniel C.
A1 Vaishampayan, Ulka
A1 Rosbrook, Bradley
A1 Fernandez, Kathrine C.
A1 Tarazi, Jamal C.
A1 George, Saby
A1 Atkins, Michael B.
YR 2020
UL http://clincancerres.aacrjournals.org/content/26/21/5598.abstract
AB 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.Patients and Methods: 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).Results: Higher baseline tumor levels of CD8 showed a trend toward longer PFS (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 IL6 was not detected at baseline had longer PFS versus 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.