Clinical utility of pembrolizumab in the management of advanced solid tumors: an evidence-based review on the emerging new data

Abstract

Pembrolizumab is a full-length human immunoglobulin G4 (IgG4) monoclonal antibody directed against the immune checkpoint PD-1 to remove its binding with PD-L1 and thus to restore an anti-tumor immune response of T cells. Pembrolizumab is one of the most advanced immune checkpoint inhibitors for cancer care. Apart from rare and serious adverse effects, its favorable tolerance profile enables to treat fragile patients who have often no other choice than best supportive care. The effective retained dose of pembrolizumab is a venous administration of 200 mg every 3 weeks until disease progression, intolerance or up to 24 months. Pembrolizumab has already proven its efficacy and thus obtained marketing authorization in so-called hot or hypermutated tumors or tumors expressing PD-L1 such as melanomas, non-small cell lung cancers, urothelial carcinomas, cervical cancer, etc. Pembrolizumab is also authorized in the United States in the treatment of mismatch repair-deficient tumors or with microsatellite instability. The current challenge is to expand its use in tumor types that are supposed to be less immunogenic, for example, by attempting to warm up the tumor microenvironment, or by combining pembrolizumab with other molecules. An acceptable toxicity profile of such combinations remains to explore. We review here the current indications of this drug, the main prognostic and predictive factors of its efficacy as well as the potential forthcoming indications.