Targeting the programmed cell death-1 pathway in breast and ovarian cancer

Purpose of review: Immune checkpoint blockade is changing cancer therapy. Targeting the programmed cell death-1 (PD-1) pathway releases T cells from inhibitory signals within the tumor microenvironment, thereby activating a latent antitumor immune response. Here, we review the biology underlying the activity of PD-1/programmed cell death-ligand 1 (PD-L1) antagonists, and data describing their clinical activity in breast and ovarian cancer. Recent findings: Several antagonists of PD-1 and PD-L1 have been tested in breast and ovarian cancer. These drugs are generally well tolerated, with some immune-related adverse events that are typically easily managed. Objective response rates generally range from about 10 to 20% in both breast cancer and ovarian cancer, with durable responses noted in multiple trials. Selecting patients with PD-L1 expression by cells within the tumor microenvironment appears to enrich for responses. These agents are under accelerated development based on these promising early data. Summary: Monoclonal antibody-based blockade of the PD-1 pathway results in objective and durable clinical responses in a subset of patients with breast or ovarian cancers, particularly those with PD-L1-positive cells within the tumor microenvironment. Current priorities are to refine biomarkers of therapeutic response, and to develop combination immunotherapy strategies that integrate PD-1/PD-L1 antagonists with both standard and immune-based cancer therapies to increase efficacy.