One treatment regimen, two different mechanisms of action
The combination of an immune checkpoint inhibitor (IO) and tyrosine kinase inhibitor (TKI) therapy acts on two pathways1
RCC is an immunogenic tumor in which PD-L1 expression can contribute to the inhibition of the antitumor response.2-8
RCC is a highly vascular tumor, in which VEGF plays a key role. VEGF acts on 3 receptors: VEGFR-1, -2, and -3, which are implicated in pathologic angiogenesis, tumor growth, and cancer progression.9
ADCC=antibody dependent cellular cytotoxicity; FcγR=Fc receptors; NK cell=natural killer cell; PD-1=programmed cell death protein 1; PD-L1=programmed death-ligand 1; VEGF=vascular endothelial growth factor; VEGFR=vascular endothelial growth factor receptor.
References: 1. Motzer RJ, Penkov K, Haanen J, et al. Avelumab plus axitinib versus sunitinib for advanced renal-cell carcinoma. N Engl J Med. 2019;380(12):1103-1115. 2. Itsumi M, Tatsugami K. Immunotherapy for renal cell carcinoma. Clin Dev Immunol. 2010. doi: 10.1155/2010/284581. 3. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy. Cancer Control. 2014;21(3):231-237. 4. Kohrt HE, Houot R, Marabelle A, et al. Combination strategies to enhance antitumor ADCC. Immunotherapy. 2012;4(5):511-527. 5. Dahan R, Sega E, Engelhardt J, Selby M, Korman AJ, Ravetch JV. FcγRs modulate the anti-tumor activity of antibodies targeting the PD-1/PD-L1 axis. Cancer Cell. 2015;28(3):285-295. 6. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent cytotoxicity. Expert Opin Biol Ther. 2017;17(4):515-523. 7. Boyerinas B, Jochems C, Fantini M, et al. Antibody-dependent cellular cytotoxicity activity of a novel anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res. 2015;3(10):1148-1157. 8. Data on file. Rockland, Mass: EMD Serono, Inc. 9. Qian C-N, Huang D, Wondergem B, The BT. Complexity of tumor vasculature in clear cell renal cell carcinoma. Cancer. 2009;115(10 suppl):2282-2289.