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

Abstract

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.

• Authors: Jean-François Martini, Elizabeth R Plimack, Toni K Choueiri, David F McDermott, Igor Puzanov, Mayer N Fishman, Daniel C Cho, Ulka Vaishampayan, Bradley Rosbrook, Kathrine C Fernandez, Jamal C Tarazi, Saby George, Michael B Atkins
• Journal: Clinical cancer research : an official journal of the American Association for Cancer Research (Clin Cancer Res) Vol. 26 Issue 21 Pg. 5598-5608 (11 01 2020) ISSN: 1557-3265 [Electronic] United States
• PMID: 32816890 (Publication Type: Clinical Trial, Phase I, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: ©2020 American Association for Cancer Research.

Chemical References

• Antibodies, Monoclonal, Humanized
• Antigens, Neoplasm
• Biomarkers, Tumor
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• IFNG protein, human
• LCN2 protein, human
• Lipocalin-2
• Receptors, Immunologic
• Interferon-gamma
• Axitinib
• pembrolizumab
• PTPN11 protein, human
• Protein Tyrosine Phosphatase, Non-Receptor Type 11
• Granzymes
• GZMA protein, human
• DDX58 protein, human
• DEAD Box Protein 58
• CA9 protein, human
• Carbonic Anhydrase IX

Topics

• Adult
• Aged
• Antibodies, Monoclonal, Humanized (administration & dosage, adverse effects)
• Antigens, Neoplasm (blood)
• Axitinib (administration & dosage, adverse effects)
• Biomarkers, Tumor (blood, genetics)
• Carbonic Anhydrase IX (blood)
• Carcinoma, Renal Cell (blood, drug therapy, genetics, 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, drug therapy, genetics, pathology)
• Progression-Free Survival
• Protein Tyrosine Phosphatase, Non-Receptor Type 11 (blood)
• Receptors, Immunologic (blood)
• Treatment Outcome