Atezolizumab for the treatment of breast cancer

ABSTRACT

Introduction: In March 2019, atezolizumab became the first immune checkpoint inhibitor to receive a breast cancer-specific approval. Based on a significant improvement in progression-free survival as well as a 10-month improvement in overall survival (on interim analysis) seen in the IMpassion 130 trial, the combination of atezolizumab and nab-paclitaxel was approved for patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC).

Areas covered: This article reviews current data and ongoing research on atezolizumab for the treatment of breast cancer. Results of atezolizumab monotherapy trials in the context of other early immune checkpoint blockade trials in breast cancer are discussed as well as data from combination clinical trials with chemotherapy in both early-stage and metastatic breast cancer. We focus on the safety and efficacy analyses from the phase III IMpassion trial that led to FDA and EMA approval of atezolizumab and nab-paclitaxel in patients whose tumor tested positive for PD-L1 by the Ventana SP142 companion diagnostic immunohistochemical assay.

Expert opinion: The FDA and EMA approvals of atezolizumab mark an important advance for treatment of metastatic TNBC. However, ongoing investigations need to define better biomarkers of response, determine resistance mechanisms, and identify strategies to increase response rates.

KEYWORDS:

• Breast cancer
• atezolizumab
• immunotherapy
• immune checkpoint blockade
• immune checkpoint inhibitor

Article highlights

• Immune checkpoint blockade has transformed the field of cancer treatment by inducing durable responses in a subset of breast cancer patients.

• The anti-PD-L1 agent atezolizumab prevents interaction between PD-L1 and its ligands (PD-1 and CD80) which ultimately releases the breaks on the immune system and enables T cell mediated tumor cell killing.

• Atezolizumab became the first FDA-approved immune checkpoint inhibitor for a breast cancer-specific indication based on results from the phase 3 IMpassion 130 trial.

• The IMpassion 130 trial demonstrated a significant progression-free survival advantage from the addition of atezolizumab to nab-paclitaxel in the frontline setting for patients with PD-L1-positive, locally advanced unresectable or metastatic TNBC.

Numerous therapeutic trials are underway focused on optimizing combination strategies and identifying biomarkers of response, to continue to build on the early success of immune checkpoint blockade in breast cancer.

Declaration of interest

SM Reddy has received support from Cancer Prevention and Research Institute of Texas RR 190,020 and has participated in advisory board for Bristol-Myers Squibb. R Nanda has served as an advisor for Aduro, AstraZeneca, Athenex, Celgene, Daiichi Sankyo, Inc, Genentech, MacroGenics, Merck, Novartis, Pfizer, Puma, and Syndax. R Nanda has served on the DSMB for G1 Therapeutics, and has received research funding from AstraZeneca, Celgene, Corcept Therapeutics, Genentech/Roche, Immunomedics, Merck, Odonate Therapeutics, Pfizer, and Seattle Genetics. R Nanda has also received support from the NIH (CA142565-06 and CA233307-01) and the Breast Cancer Research Foundation. 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.

Reviewer disclosures

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

Additional information

Funding

This paper received no funding.