Enhertu (Trastuzumab Deruxtecan) Treatment of HER2+ Breast Cancer: Understanding Benefits and Lung Toxicity

Concerning Lung Toxicity Identified with Enhertu for HER2-positive Metastatic Breast Cancer – FDA Approves with “black box warning” for HER2 “low” disease. This powerful treatment has shown promising results in patients, but recent findings have also highlighted lung toxicity concerns. In this article, we will explore the benefits and potential risks associated with Enhertu (trastuzumab deruxtecan) treatment for HER2+ breast cancer.

The United States Food and Drug Administration initially approved Enhertu (trastuzumab deruxtecan) (DS-8201) for the treatment of patients with HER2-positive metastatic breast cancer in 2019. Enhertu is a HER2-targeting antibody drug conjugate (ADC) used for the treatment of patients with advanced HER2-positive cancer. Recent research suggests Enhertu is very effective for treating cancer that has spread to the brain or central nervous system and for patients with minimal or “low” HER2 expression that historically were not offered HER2 directed therapy.

Updated data released at the 2022 American Society of Clinical Oncology Annual Meeting suggests lung toxicity continues to be a problem. In a comparative trial, the rates of treatment-related interstitial lung disease (ILD)/pneumonitis were 11% with Enhertu compared to 2% with Kadcyla (trastuzumab emtansine).

About Enhertu (trastuzumab deruxtecan)

ADCs are a type of targeted cancer medicine that deliver cytotoxic chemotherapy (“payload”) to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells. Enhertu is a smart chemotherapy comprised of a humanized HER2 antibody attached to a novel topoisomerase I inhibitor (DXd) payload by a tetrapeptide linker. It is designed to deliver enhanced cell destruction upon release inside the cell and reduce systemic exposure to the cytotoxic payload (or chemotherapy) compared to the way chemotherapy is commonly delivered.

The results of the initial breast cancer trial reported that an objective response rate of 60%, a disease control rate of 94% and an average survival duration of 21 was attained at the recommended dose of Enhertu in patients treated with an average of seven prior lines of treatment.

Enhertu Superior to Kadcyla in patients with HER2-positive metastatic breast cancer

The DESTINY-Breast 03 Phase III clinical trial evaluated the safety and effectiveness of Enhertu versus Kadcyla (trastuzumab emtansine (T-DM1) in ~500 patients with HER2-positive unresectable and/or metastatic breast cancer previously treated with trastuzumab and a taxane. Data released in December 2022 showed that the  median survival duration without cancer progression was improved from 7 months with T-DM1 to 29 months for individuals treated with Enhertu. The objective response rate for patients on Enhertu was 79%, compared to 34% for those on T-DM1.

For full article: Cancerconnect – Enhertu Trastuzumab Deruxtecan

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