Avelumab for the treatment of patients with Merkel cell carcinoma

Abstract

Merkel cell carcinoma is a rare and aggressive skin tumor that is difficult to treat even at early stages. Treatment approaches for advanced disease are limited and standard chemotherapy provides short-lived disease control in half of patients without significant impact on the overall survival. The new immunotherapy with anti-PD-1/PD-L1 inhibitors allows to improve clinical outcomes of this disease. Avelumab is a fully human IgG1 monoclonal anti- PD-L1 antibody that blocks the interaction between programmed cell death ligand 1 (PD-L1) on tumor cells and programmed cell death-1 receptor (PD-1) on T cells, thereby elimination immunosuppression in the tumor microenvironment. Avelumab provides disease control in 43,2% of the patients with metastatic/locally advanced unresectable Merkel cell carcinoma for the second and subsequent lines treatment with the objective response rate (ORR) 33%. The response was ongoing for ≥ 6 months in 86% of patient with median duration of response 40,5 months. Responses occurred irrespectively of PD-L1 expression and presence of polyomavirus in tumor cells (MCPyV), 3-year overall survival rate reached 32%. Avelumab is more effective for the first line of treatment, providing the disease control in 78,6% the patients with ORR 71,5% lasting for ≥ 6 months. Treatment is well tolerated for the first, second and subsequent lines, demonstrating the adequate safety profile. The most common adverse events were fatigue, diarrhea and nausea. There were 7 patients in Russia treated with avelumab for metastatic/locally advanced unresectable Merkel cell carcinoma.

Keywords

• merkel cell carcinoma
• avelumab
• anti-pd-l1
• pd-l1 expression
• chemotherapy