Pembrolizumab in cervical cancer: latest evidence and clinical usefulness

Abstract

Cervical cancer is the fourth most common cause of cancer-related deaths in women worldwide. With the development of detection of precancerous lesions and preventive human papillomavirus (HPV) vaccination program, a survival improvement has been observed in these patients in developed countries, although disparities in accessibility to treatments exist across countries. While early-stage cervical cancer can be curable with surgery, prognosis of patients who recur remains poor, with limited treatment options. In this latter setting, recently, bevacizumab, an antiangiogenic monoclonal antibody targeting vascular endothelial growth factor (VEGF), has been shown to improve overall survival in combination with chemotherapy as compared with chemotherapy alone. No standard treatments exist beyond this treatment regimen. New effective treatments are therefore much needed in this setting. Immunotherapy has represented a breakthrough in recent years in oncology, with antitumor activity reported with immune-checkpoint inhibitors in a variety of tumor types. We discuss here the latest evidence and clinical usefulness of pembrolizumab, anti-PD-1 checkpoint inhibitor, in the treatment of advanced cervical cancer.

Keywords: cervical cancer; immune checkpoints; immunotherapy; pembrolizumab.

Figure 1.

Mechanism of action of anti-programmed-cell-death-protein-1 antibody in cervical cancer. HPV, human papillomavirus; MCH I, major histocompatibility complex I; TCR, T-cell receptor; PD-1, programmed-cell-death-protein 1; PD-L1, PD-1 ligand 1. Neoantigens, such as cancer antigens or viral antigen in HPV-related cancer, are recognized by T cells via antigens-presenting cells, leading to T-cell activation. Immunotolerance in the tumoral microenvironment includes PD-1 overexpression on tumoral-infiltrating lymphocytes and PD-L1 overexpression on tumor cells, leading to the inhibition of activated effector T cells, via inhibitory checkpoint signals. By inhibiting the interaction between PD-1 and PD-L1, anti-PD-1/PD-L1 antibodies block the inhibitory checkpoint signals and restore endogenous antitumor immunity.