A New Standard of Care: Pembrolizumab in Programmed Death-ligand 1 Positive, Metastatic, Triple-negative Breast Cancer

Abstract

Metastatic triple-negative breast cancer (mTNBC) carries a poor prognosis, with a median survival of 1–2 years. Despite multiple attempts at using immunotherapy in this patient population, it was only in recent years that large-scale clinical trials, studying immune checkpoint inhibitors (ICI) in mTNBC, have emerged with promising data. First came approval from the US Food and Drug Administration (FDA) in 2017 for the use of pembrolizumab in solid tumours found to be either microsatellite instability high or mismatch repair deficient, illuminating the potential role of immunotherapy in select patients with breast cancer. Then in 2019, following the results of the IMpassion130 trial, atezolizumab became the first ICI approved for use in breast cancer, specifically as combination therapy with nab-paclitaxel for patients with programmed death-ligand 1 (PD-L1)-positive mTNBC. In early 2020, pembrolizumab was approved for use in solid tumours with a high tumour mutational burden, which represents a small population of breast cancer patients. In late 2020, based upon the results of the KEYNOTE-355 trial, the FDA approved pembrolizumab for use in combination with conventional chemotherapy for PD-L1-positive mTNBC, specifically in patients found to have tumours with a combined positive score ≥10. Outside of mTNBC, pembrolizumab has also received FDA approval for use in high-risk, early-stage triple-negative breast cancer (TNBC) as of July 2021, following the regulatory release of KEYNOTE-522 which demonstrated improved outcomes when used in combination with neoadjuvant chemotherapy, followed by adjuvant pembrolizumab monotherapy. This review will focus on the details surrounding these landmark trials and discuss how pembrolizumab has become integrated into the new standard of care for patients with PD-L1-positive mTNBC.