PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma

Merkel-cell carcinoma is an aggressive neuroendocrine tumor that is poorly responsive to chemotherapy. In a small series of patients, pembrolizumab produced responses in a majority of patients, including some complete responses. The programmed death 1 (PD-1) immune checkpoint pathway, which comprises the PD-1 T-cell coinhibitory receptor and its ligands PD-L1 and PD-L2 expressed on tumor and immune cells in the tumor microenvironment, mediates local immune resistance. 1 Monoclonal antibodies blocking this pathway are active against advanced tumors of several different types, providing a “common denominator” for cancer therapy. 2 PD-L1 expression in pretreatment tumor specimens may identify patients and tumor types that are more likely to have a response to PD-1 pathway blockade, and PD-L1 immunohistochemical tests were recently approved by the Food and Drug Administration to guide clinical decision making for patients . . .