Mechanistic Differences Between PD-1 and PD-L1 Blockade

Dr Whitman introduces cosibelimab, the third checkpoint inhibitor approved in advanced cutaneous squamous cell carcinoma, and the faculty examine what distinguishes it mechanistically from cemiplimab and pembrolizumab. Because cosibelimab binds PD-L1 rather than PD-1, the faculty walk through how the two blockade strategies differ at the level of receptor and ligand interaction, and what those differences may or may not mean clinically. Dr In explains why PD-L1 blockade leaves certain signaling interactions intact while PD-1 blockade does not. The faculty then compare reported efficacy across the three approved agents, including objective response rates and the depth and quality of responses observed in pivotal trials. Both conclude that the available data do not meaningfully separate the agents on efficacy, with Dr Whitman noting a reasonable argument can be made that they are virtually identical in clinical benefit for most patients with advanced disease.