DESTINY-Breast15

In this poster from SABCS 2023, Prof Antonio Llombart, Head of department of Medical Oncology at the University Hospital Arnau de Vilanova in Valencia, presents the DESTINY-Breast15 study. This study will be conducted to assess T-DXd in patients with HR+ or HR− metastatic breast cancer with low or no measurable tumour HER2 expression.

DESTINY-Breast15 aims to contribute to the comprehensive understanding of what is termed HER2-0 and its association with the efficacy of trastuzumab deruxtecan. The study encompasses four distinct cohorts comprising patients with luminal or triple-negative breast cancer, specifically categorised as HER2-0 or HER2-low. Stringent inclusion criteria require patients to be endocrine-resistant, particularly for luminal tumours, and limit prior treatments to no more than two lines, including any form of endocrine therapy. The study emphasises the necessity of capturing a substantial proportion of tumour samples.

Patients entering the study are obligated to undergo a biopsy before participation. Additionally, the study recommends obtaining another biopsy from the patient’s metastatic history, and subsequent biopsies are scheduled after two treatment cycles. Plasma samples will also be collected at various points throughout the study.

In the event of a promising clinical signal for both HER2-0 and HER2-low cohorts, the study proposes initiating an extensive pathology and biomarker program. The objective is to employ alternative methods beyond immunohistochemistry to accurately identify patients who genuinely respond to trastuzumab deruxtecan and exhibit HER2 zero or ultra-low expression. This study represents a strategic effort to refine the characterisation of HER2 status and optimise treatment outcomes with trastuzumab deruxtecan.

Reference:

Modi S. et al., An Open-label, Interventional, Multicenter Study of Trastuzumab Deruxtecan Monotherapy in Patients With Unresectable and/or Metastatic HER2-Low or HER2 Immunohistochemistry 0 Breast Cancer: DESTINY-Breast15 – SABCS 2023, # PO2-19-06