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

ABSTRACT

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.

KEYWORDS:

• Immunotherapy
• triple-negative breast cancer

Article Highlights

• Patients with triple-negative breast cancer (TNBC) have a more aggressive disease course, higher risk of metastatic recurrence and limited systemic treatment options compared to other breast cancer subtypes.

• TNBC has a higher tumor mutational burden, expression of tumor-infiltrating lymphocytes (TILs) and PD-L1 expression compared to other breast cancer subtypes, supporting the potential activity of immunotherapy.

• The addition of atezolizumab to nab-paclitaxel prolonged progression-free survival (PFS) in the intent-to-treat population and in the PD-L1-positive subgroup of patients in the first-line treatment of metastatic TNBC with low rates of severe autoimmune toxicity.

• Atezolizumab plus nab-paclitaxel should be considered in appropriate patients without clinically significant autoimmune disease with metastatic PD-L1-positive TNBC.

Declaration of interest

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewers Disclosure

Peer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.

Additional information

Funding

This investigation was supported by the National Institutes of Health under Ruth L. Kirschstein National Research Service Award T32CA236734–01. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH.