Atezolizumab in the treatment of metastatic triple-negative breast cancer

ABSTRACT

Introduction

Triple-negative breast cancer (TNBC) accounts for approximately 10%-15% of all diagnosed breast cancers and is associated with an aggressive natural history and poor clinical outcomes. Immunotherapy using immune checkpoint inhibitors has emerged as an effective therapeutic option for TNBC. The results of the IMpassion130 trial have recently led to the approval of the combination of atezolizumab and nab-paclitaxel in the first-line treatment of patients with unresectable locally advanced or metastatic, PD-L1-positive TNBC.

Areas covered

This article summarizes the clinical development and ongoing research on atezolizumab in the treatment of metastatic TNBC. Results of atezolizumab monotherapy trials and data from combination studies with chemotherapy in the advanced setting are reviewed, with special focus on the design, methods, and key findings of the IMpassion130 trial.

Expert opinion

The approval of atezolizumab plus nab-paclitaxel represents an important advance in the treatment of metastatic TNBC. This combination has a favorable risk-benefit profile and is associated with clinically meaningful outcomes. However, further research is needed to identify better predictive biomarkers of response as well as novel immunotherapeutic strategies with atezolizumab and other anticancer drugs.

KEYWORDS:

• Triple-negative breast cancer
• immunotherapy
• immune checkpoint inhibitors
• PD-1/PD-L1 axis
• atezolizumab

Article highlights

• Multiple lines of evidence have shown that tumor cells can evade destruction by the immune system by expressing surface ligands that engage inhibitory receptors on tumor-specific T cells and induce immune tolerance.

• Immunotherapy using immune checkpoint inhibitors has emerged as an important therapeutic option in cancer treatment, including breast cancer.

• The results of the IMpassion130 phase 3 trial have led to atezolizumab in combination with nab-paclitaxel becoming the first approved regimen for breast cancer to include immunotherapy.

• This regimen is the preferred first-line treatment for patients with unresectable locally advanced or metastatic, PD-L1-positive TNBC.

• To select patients with metastatic TNBC who will derive the greatest clinical benefit from adding atezolizumab to standard first-line chemotherapy, PD-L1 testing should be performed using the same assay and definition used in the IMpassion130 trial.

• The addition of atezolizumab to first-line chemotherapy is recommended if at least one tumor sample (primary tumor or metastatic site) shows PD-L1 positivity.

• New predictive biomarkers of response and new combination strategies with atezolizumab and other antineoplastic agents for the treatment of TNBC are currently being evaluated in ongoing studies.

This box summarizes key points contained in the article.

Acknowledgments

The authors received medical writing support in the preparation of this manuscript from Dr. Luis F. García-Fernández (Medical Statistics Consulting, S.L., Valencia, Spain).

Declaration of interest

J Cortés reports consultant fees from Athenex, Biothera Pharmaceuticals, Cellestia, Daiichi Sankyo, Erytech, Merus, Lilly, Pholypor, Seattle Genetics and Servier; personal fees from Novartis, Pfizer and Samsung; grants from Ariad Pharmaceuticals, Baxalta GMBH/Servier Affaires, Bayer HealthCare, F. Hoffman-La Roche, Guardanth Health,

Merck Sharp & Dohme (MSD), Pfizer, Piqur Therapeutics, Puma Biotechnology, and Queen Mary University of London; consultant fees, personal fees, and grants from Roche; consultant fees and personal fees from Celgene; consultant fees and grants from AstraZeneca; personal fees and grants from Eisai; intellectual property rights and patent holding and ownership interests in MedSIR. J Pérez-García reports consultant fees from Roche and Lilly. J Soberino reports personal fees and travel grants from Roche; personal fees from Eisai; and travel grants from Merck Sharp & Dohme (MSD). A Stradella reports personal fees and non-financial support from Roche, Celgene and Eisai; non-financial support from Pfizer. 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

One of the reviewers of this manuscripts institute receives research funding from Roche, AZ, and BMS. Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.

Correction Statement

This article has been republished with minor changes. These changes do not impact the academic content of the article.

Notes

1. See ClinicalTrials.gov for trial details: NCT02685059 (GeparNuevo), NCT02622074 (KEYNOTE-173), NCT03036488 (KEYNOTE-522), NCT01042379 (I-SPY 2), NCT03197935 (IMpassion031), NCT03281954 (GeparDouze), NCT02620280 (NeoTRIPaPDL1), and NCT03498716 (IMpassion030).

Additional information

Funding

This paper was not funded.