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

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.

Evidences of CTLA-4 and PD-1 Blocking Agents-Induced Cardiotoxicity in Cellular and Preclinical Models

“…Immune checkpoint inhibitors (ICIs) improved overall survival in patients with cancer, opening up a new era in oncology in the last five years [ 1 , 2 ]. ICIs include blocking antibodies against programmed death 1 (PD-1) such as Nivolumab and Pembrolizumab [ 3 , 4 ]; programmed death ligand 1 (PD-L1) with Atezolizumab, Avelumab, and Durvalumab [ 5 , 6 , 7 ], or cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitors like Tremelimumab and also Ipilimumab [ 8 , 9 ]. However, several mechanisms are involved in immune system homeostasis as well as in cancer immune tolerance and immune-resistance, and some patients differ in PD-1 or CTLA4 expression, so different strategies are under study in clinical oncology [ 10 ].…”

High-Risk HPV Oncoproteins and PD-1/PD-L1 Interplay in Human Cervical Cancer: Recent Evidence and Future Directions

“…In this context, pembrolizumab, an immune checkpoint inhibitor, represents a full-length human IgG4/kappa monoclonal antibody that is directed against the PD-1 protein ( 60 , 61 ) and has been approved by the FDA as a second-line treatment for recurrent or metastatic carcinomas of the cervix, non-small cell lung, and urothelial as well as malignant melanoma ( 60 ). Pembrolizumab (Keytruda) was approved for the treatment of patients with recurrent and/or metastatic cervical cancer in 2018 based on the KEYNOTE 158 (NCT02628067) Phase II study which involved 98 patients with recurrent and/or metastatic cervical carcinomas ( 62 ).…”

The LEAP Program: Lenvatinib Plus Pembrolizumab for the Treatment of Advanced Solid Tumors

“…PD-1 inhibition by pembrolizumab counteracts the downregulation of the antitumor immune response mediated by the PD-1 pathway [6]. Pembrolizumab is administered by intravenous infusion and is currently indicated for a broad spectrum of solid and hematologic cancers (Table 1) [6,22].…”