Trastuzumab Deruxtecan for HER2+ Advanced Breast Cancer

Abstract

Trastuzumab deruxtecan (T-DXd, DS-8201), an anti-HER2 antibody–drug conjugate, has shown significant clinical benefits in HER2+ metastatic breast cancer patients. In the phase 2 DESTINY-Breast01 trial, T-DXd demonstrated an objective response of 60.9% and median progression-free survival of 16.4 months, laying the foundation for accelerated approval in HER2+ metastatic breast cancer patients who have received two or more prior anti-HER2-based regimens in the metastatic setting. Moreover, T-DXd exhibited promising antitumor efficacy against HER2-low-expressing metastatic breast cancer. Its distinctive side effect was pneumonitis, with a 13.6% incidence. It is approved in the US with boxed warnings for interstitial lung disease and embryo–fetal toxicity. This review focuses on preclinical, pharmacokinetic and pharmacodynamic data on T-DXd and clinical evidence of its antitumor activity (both as monotherapy and in combination) and tolerability in metastatic breast cancer.

Lay abstract

Breast cancer can be grouped based on its HR and HER2 status. For patients with HER2+ breast cancer, treatments that fight HER2 portion are adopted. Trastuzumab deruxtecan (DS-8201) is a new drug that consists of two parts: a cytotoxic drug and anti-HER2 antibody. It can selectively target HER2-expressing tumor cells. In a recent clinical trial, trastuzumab deruxtecan demonstrated tumor shrinkage in six of ten patients. The time to increase in tumor size or death was 16 months. Its antitumor effect was also demonstrated in low-HER2-expressing breast cancer. Approximately 13% of patients experience lung inflammation following trastuzumab deruxtecan treatment. In these cases, the drug should be promptly halted and the doctor can start steroid therapy.

Keywords::

• breast cancer
• DESTINY-Breast01
• DS-8201
• HER2
• T-DXd
• trastuzumab deruxtecan

Financial & competing interests disclosure

The authors have no 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending or royalties.

No writing assistance was utilized in the production of this manuscript.

Company review disclosure

In addition to the peer-review process, with the authors' consent, the manufacturer of the product discussed in this article was given the opportunity to review the manuscript for factual accuracy. Changes were made by the authors at their discretion and based on scientific or editorial merit only. The authors maintained full control over the manuscript, including content, wording and conclusions.