ABSTRACT
Immune checkpoint antibodies that augment the programmed cell death protein 1 (PD-1)/PD-L1 pathway have demonstrated antitumor activity across multiple malignancies, and gained recent regulatory approval as single-agent therapy for the treatment of metastatic malignant melanoma and nonsmall-cell lung cancer. Knowledge of toxicities associated with PD-1/PD-L1 blockade, as well as effective management algorithms for these toxicities, is pivotal in order to optimize clinical efficacy and safety. In this article, we review selected published and presented clinical studies investigating single-agent anti-PD-1/PD-L1 therapy and trials of combination approaches with other standard anticancer therapies, in multiple tumor types. We summarize the key adverse events reported in these studies and their management algorithms.
Subject(s)
Antibodies, Monoclonal/adverse effects , Antibodies, Monoclonal/immunology , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/immunology , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/immunology , Animals , Antibodies, Monoclonal/pharmacology , Exanthema/chemically induced , Fatigue/chemically induced , Humans , Neoplasms/drug therapy , Neoplasms/immunology , Pneumonia/chemically inducedABSTRACT
BACKGROUND: Immune modulation in cancer refers to a range of treatments aimed at harnessing a patient's immune system to achieve tumour control, stabilisation, and potential eradication of disease. A novel therapeutic drug class called immune checkpoint-blocking antibodies modulate T-cell pathways that regulate T cells and have the potential to reinvigorate an antitumour immune response. Ipilimumab was the first FDA-approved immune checkpoint antibody licensed for the treatment of metastatic melanoma (MM) and blocks a checkpoint molecule called cytotoxic T-lymphocyte antigen 4 (CTLA-4). METHODS: Herein we review the preclinical and clinical development of ipilimumab. We outline the mode of action of these agents and other immune checkpoint inhibitors, the management of their toxicities, and how to adequately assess response to treatment. RESULTS: As a result of these data, a number of other antibodies that block novel checkpoint molecules including programmed death-1 (PD-1), and corresponding ligands such as programmed death ligand-1 (PD-L1) are under preclinical and clinical development, and have demonstrated activity in multiple tumour types. CONCLUSIONS: This review will summarise the mechanism of action and clinical development of immune checkpoint antibodies, as well as lessons learned in the management and assessment of patients receiving these agents.
