Antibody-drug conjugates, immune-checkpoint inhibitors, and their combination in breast cancer therapeutics

ABSTRACT

Introduction

Advanced breast cancer (aBC) remains incurable and the quest for more effective systemic anticancer agents continues. Promising results have led to the FDA approval of three antibody–drug conjugates (ADCs) and two immune checkpoint inhibitors (ICIs) to date for patients with aBC.

Areas covered

With the anticipated emergence of newer ADCs and ICIs for patients with several subtypes of breast cancer, and given their potential synergy, their use in combination is of clinical interest. In this article, we review the use of ADCs and ICIs in patients with breast cancer, assess the scientific rationale for their combination, and provide an overview of ongoing trials and some early efficacy and safety results of such dual therapy.

Expert Opinion

Improvement in the medicinal chemistry of next-generation ADCs, their rational combination with ICIs and other agents, and the development of multiparametric immune biomarkers could help to significantly improve the outlook for patients with refractory aBC.

KEYWORDS:

• Breast cancer
• antibody–drug conjugate
• immune checkpoint inhibitor
• bystander effect
• atezolizumab
• pembrolizumab
• sacituzumab govitecan
• trastuzumab deruxtecan
• trastuzumab emtansine
• dual therapy

Article highlights

• Advance breast cancer (aBC) remains incurable, and newer and more effective systemic anticancer agents are needed.

• Antibody-drug conjugates (ADCs) have an established role, with the US FDA having approved trastuzumab emtansine, trastuzumab deruxtecan, and sacituzumab govitecan in different breast cancer settings.

• Immune checkpoint inhibitors (ICIs) also have encouraging activity, and the US FDA has approved atezolizumab and pembrolizumab for patients with PD-L1-positive aBC.

• There is a scientific rationale and clinical interest in combining ADCs and ICIs in patients with aBC.

• We review ADCs, ICIs, and their use in combination, and discuss the clinical results to date in patients with breast cancer.

Declaration of interest

Kamal S Saini: Consulting fees from the European Commission outside the submitted work. Kevin Punie: Honoraria for advisory/consultancy roles for AstraZeneca, Eli Lilly, Gilead Sciences, Medscape, MSD, Novartis, Pfizer, Pierre Fabre, Hoffmann/La Roche, Teva and Vifor Pharma (paid to institution); speaker fees for Eli Lilly, MSD, Mundi Pharma, Novartis, Pfizer and Hoffmann/La Roche (paid to institution); research funding from Sanofi (paid to institution); and travel support from AstraZeneca, Novartis, Pfizer, PharmaMar and Hoffmann/La Roche; all outside the submitted work. Chris Twelves: Consultancy fees AstraZeneca, Daiichi Sankyo, Eisai, Pfizer; Speakers fees Eisai, Pfizer; Travel MSD, Eisai, Roche/Genentech; all outside the submitted work. Evandro de Azambuja: honoraria and advisory board: Roche/GNE, Novartis, Seattle Genetics, Zodiacs, Libbs and Pierre Fabre; travel grants: Roche/GNE, GSK/Novartis. Research grant for his institute: Roche/GNE, AstraZeneca, Novartis, and Servier; all outside the submitted work. Ahmad Awada: Advisory role, research grants to my Institute, speaker fees: Roche, Lilly, Amgen, Eisai, BMS, Pfizer, Novartis, MSD, Genomic Health, Ipsen, AstraZeneca, Bayer, Leo Pharma; all outside the submitted work. Sherene Loi: Research funding to institution from Novartis, Bristol Meyers Squibb, Merck, Puma Biotechnology, Eli Lilly, Nektar Therapeutics, AstraZeneca and Seattle Genetics; consultant (not compensated) to Seattle Genetics, Novartis, BMS, Merck, AstraZeneca and Roche-Genentech; consultant (paid to her institution) to Aduro Biotech, Novartis, GlaxoSmithKline, Roche-Genentech, AstraZeneca, Silverback Therapeutics, and G1 Therapeutics; Scientific Advisory Board Member of Akamara Therapeutics; and supported by the National Breast Cancer Foundation of Australia Endowed Chair and the Breast Cancer Research Foundation, New York; all outside the submitted work. 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 relationships or otherwise to disclose.

Additional information

Funding

This paper is not funded.