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Observational Study
. 2024;20(18):1237-1250.
doi: 10.2217/fon-2024-0015. Epub 2024 Apr 9.

Study design for DESTINY-Breast Respond HER2-low Europe: T-DXd in patients with HER2-low advanced breast cancer

Valentina Guarneri  1   2 , José Luís Passos Coelho  3 , Francois P Duhoux  4 , Daniel Egle  5 , José Ángel García-Sáenz  6 , Frédérique Penault-Llorca  7 , Katri Selander  8   9 , Hans Wildiers  10 , Khalil Zaman  11 , Petra Laeis  12 , Markus Lucerna  12 , Jean-Yves Pierga  13
Affiliations
Observational Study

Study design for DESTINY-Breast Respond HER2-low Europe: T-DXd in patients with HER2-low advanced breast cancer

Valentina Guarneri et al. Future Oncol. 2024.

Abstract

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.

Keywords: HER2-low; adverse events; metastatic breast cancer; overall survival; patient-reported outcomes; progression-free survival; trastuzumab deruxtecan.

Plain language summary

Trastuzumab deruxtecan (T-DXd; Enhertu®) 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.Clinical Trial Registration: ICH CGP: NCT05945732, registered on 6 July 2023 (ClinicalTrials.gov).

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Conflict of interest statement

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 above. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Figures

Figure 1.
Figure 1.
Study design. a Documentation of some information collected at baseline (e.g., prior medication, prior SEIs, comorbidities) refers to a time period 6 months before study start date. b Selected gastrointestinal toxicity of interest, including nausea and vomiting, will be assessed via daily diaries. c PRO measured via validated questionnaire. EoS: End of study; PRO: Patient-reported outcome; SEI: Safety event of interest; SOC: Standard of care; T-DXd: Trastuzumab deruxtecan.
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