Tackling metastatic triple-negative breast cancer with sacituzumab govitecan.

Introduction Metastatic triple-negative breast cancer (TNBC) is an aggressive cancer with poor survival that is difficult to treat due to a lack of targeted options. Conventional therapies targeting hormone receptors (HR) and human epidermal growth factor 2 (HER2) are ineffective and often chemotherapy is standard-of-care. Sacituzumab govitecan is an antibody drug conjugate (ADC) comprised of an active metabolite of irinotecan, SN-38, bound to a humanized monoclonal antibody targeting trophoblastic cell-surface antigen 2 (Trop-2). Trop-2 is highly expressed on the surface of TNBC cells, making it an attractive target. Areas covered We explore the mechanism, pharmacology, efficacy, safety, and tolerability of sacituzumab govitecan. A literature search was conducted via PubMed using keywords such as 'sacituzumab govitecan,' and 'metastatic TNBC.' Expert opinion Sacituzumab govitecan has promising survival benefits in patients with previously treated mTNBC based on data from the ASCENT trial. Common adverse effects were neutropenia, diarrhea, and nausea, however these effects were manageable with supportive care. Sacituzumab govitecan has shown promise in cancers outside of TNBC, such as urothelial and lung and is being evaluated in HR-positive breast cancers. It is likely we will see this therapy used in combination with other novel targeted agents as current clinical trials mature.

Nab-paclitaxel and atezolizumab for the treatment of PD-L1-positive, metastatic triple-negative breast cancer: review and future directions.

INTRODUCTION: Breast cancer is the most common malignancy in women in the United States and triple-negative breast cancer (TNBC) accounts for 15-20%. The standard of care for metastatic TNBC has been limited to cytotoxic chemotherapy with modest efficacy. TNBC is associated with high levels of tumor-infiltrating lymphocytes and PD-L1 expression, supporting the investigation of immune checkpoint inhibitors in this breast cancer subtype. AREAS COVERED: This review summarizes the clinical data supporting the use of atezolizumab and nab-paclitaxel in the treatment of metastatic PD-L1-positive TNBC. It examines the pharmacology and toxicity profile of the combination in patients with metastatic TNBC. EXPERT OPINION: The addition of atezolizumab to nab-paclitaxel prolonged progression-free survival in both the intention-to-treat and PD-L1-positive subgroups in the first line setting in patients with metastatic TNBC. The IMpassion 130 trial led to FDA-approval of this combination in patients with PD-L1-positive, metastatic TNBC and represents the first approval of immunotherapy for TNBC. This work supports ongoing investigations of other immunotherapy combinations in TNBC, predictive biomarker development and immunotherapy in patients with early stage TNBC. Immunotherapy combinations in TNBC have the potential to lead to improved survival in this group of patients with high risk disease.