Study design for DESTINY-Breast Respond HER2-low Europe: T-DXd in patients with HER2-low advanced breast cancer
Creators: name: Guarneri, Valentina
name: Coelho, José Luís Passos
name: Duhoux, Francois P
name: Egle, Daniel
name: García-Sáenz, José Ángel
name: Penault-Llorca, Frédérique
name: Selander, Katri
name: Wildiers, Hans
name: Zaman, Khalil
name: Laeis, Petra
name: Lucerna, Markus
name: Pierga, Jean-Yves
Publisher: name: Taylor & Francis
Year: 2024
Subjects: subject: Medicine
subject: Pharmacology
subject: Biotechnology
subject: Biological Sciences not elsewhere classified
subject: Cancer
subject: Science Policy
subject: Plant Biology
subject: FOS: Biological sciences

description: Trastuzumab deruxtecan (T-DXd) is approved for the treatment of human epidermal growth factor receptor 2 (HER2)-low metastatic breast cancer (mBC). Results on T-DXd treatment in HER2-low mBC have so far been limited to clinical trials. DESTINY-Breast Respond HER2-low Europe (NCT05945732) is a multi-center, multi-country, observational, prospective, non-interventional study planning to enroll 1350 patients from 216 sites receiving T-DXd or conventional chemotherapy as their routine clinical care for advanced stage breast cancer in 12 European countries. This non-interventional study will provide real-world insight into T-DXd treatment for HER2-low mBC with data on effectiveness, safety and tolerability, patient-reported outcomes, treatment patterns, geriatric health status and HER2 testing. This will be beneficial for improving guidance to maximize patient treatment benefit. Trastuzumab deruxtecan (T-DXd; Enhertu<sup>®</sup>) is a medicine approved to treat cancers that produce a protein called HER2 on the surface of cancer cells. T-DXd works by targeting the HER2 protein to deliver chemotherapy directly to cancer cells. Until recently, breast cancers were classified as HER2-positive (high level of HER2 protein on cancer cells) or HER2-negative (very low level/no HER2 protein on cancer cells). T-DXd was approved for treating patients with HER2-positive advanced breast cancer in Europe in 2022. In 2023 the DESTINY-Breast04 clinical trial showed that T-DXd was more effective than current standard chemotherapies, when treating advanced breast cancer patients with low levels of the HER2 protein (historically classified as HER2-negative cancer). This trial led to the approval of T-DXd for treating advanced HER2-low breast cancer, providing a new treatment option for 50–60% of breast cancer patients. More information is needed about T-DXd treatment in the real world (for patients treated in the hospital, rather than in a clinical trial). This article describes the purpose and design of the DESTINY-Breast Respond HER2-low Europe study, which will collect and report more information about how effective T-DXd treatment is in the real world. This is a large study aiming to include 1350 eligible patients from 12 countries across Europe. Patients will report their experience of side effects (such as nausea and vomiting) to improve management of T-DXd treatment and maximize patient benefit. The study will also examine how elderly patients respond to T-DXd treatment, and how HER2 levels are being tested. <b>Clinical Trial Registration</b>: ICH CGP: NCT05945732, registered on 6 July 2023 (ClinicalTrials.gov) DESTINY-Breast Respond HER2-low Europe (NCT05945732) is a multi-center, multi-country, observational, prospective, non-interventional study (NIS) of trastuzumab deruxtecan (T-DXd) in patients with HER2-low mBC. The study will provide information about T-DXd effectiveness, safety and tolerability, PROs and treatment patterns. The study will include a disease registry of patients treated with conventional chemotherapy to contextualize treatment patterns and effectiveness of T-DXd and conventional chemotherapy. The study will include a geriatric screening to provide data around T-DXd use in older patients. HER2 testing practices across different European countries will be examined through pathologist surveys. Approximately 1350 patients will be enrolled from 216 sites in 12 European countries. The study is planned to take place between 2023 and 2028.