HER 2 Low-expressing Breast Cancer

This is a phase II, multicentre, open-label, randomised controlled trial (patients are randomly assigned to one treatment arm or the other) evaluating two treatment strategies (sacituzumab govitecan and trastuzumab deruxtecan in an alternative schema or sacituzumab govitecan alone) in patients with locally advanced or metastatic triple-negative breast cancer. The goal is to answer the question: Does alternating sacituzumab goveitecan (SG) and trastuzumab deruxtecan (T-DXd) improve survival in patients with HER2-low metastatic triple-negative breast cancer compared to continuing treatment with SG alone?

The purpose of this study is to determine if the radiotracer, \[68Ga\]Ga-ABY-025, used for PET imaging can help us better identify and visualize lesions or tumors, in patients who are receiving standard of care therapy HER2+ cancers.

The development of trastuzumab deruxtecan (T-DXd), an anti-HER2 conjugated antibody, has changed the therapeutic landscape of breast cancer. Anti-HER2 molecules were previously used exclusively in cases of HER2-positive breast cancer (IHC HER2 3+ or HER2 2+ with amplified FISH/SISH). Since a couple of years, T-DXd is becoming a reference treatment in patients with low HER2 breast cancer (IHC 1+ or 2+ with non-amplified FISH/SISH) after hormone therapy and at least one line of chemotherapy. The results of the DB04 trial revealed that T-DXd increased progression-free survival and overall survival compared to investigator's choice chemotherapy, in HER2 low breast cancers patients after one or two previous lines of chemotherapy (Modi, S. et al., 2022). In several trials, T-DXd validation was done thanks to radiological evaluation based on conventional imaging, computed tomography scan (CT-scan) with or without contrast dye injection and bone scintigraphy. 18F-Fluorodeoxyglucose positron emission tomography coupled with computed tomography (18F-FDG PET-CT) represents a major tool for diagnosis, staging, and therapeutic follow-up in oncology. It was demonstrated that 18F-FDG PET-CT is more sensitive in detecting metastatic disease progression in HER2-positive breast cancer patients treated with trastuzumab and pertuzumab or trastuzumab and lapatinib (Ma, G. et al., 2023 et Lin, N. U. et al., 2015). Moreover, a prospective study investigated the correlation between the response rate defined by 18F-FDG PET-CT and thoraco-abdomino-pelvic CT-scan (TAP CT-scan) and the progression-free survival of patients with breast cancer. PET evaluation allowed better identification of responders versus non-responders, with a significant correlation with progression-free survival (Vogsen, M. et al., 2023). With this study, the investigators aim to determine the role of 18F-FDG PET-CT in evaluating T-DXd treatment in patients with metastatic low HER2 breast cancer. 18F-FDG PET-CT could be an earlier evaluation tool than CT-scan in identifying non-responsive patients; and thus, avoid continuing an expensive treatment with an unfavorable toxicity profile, which could worsen both patient prognosis and quality of life.

Breast cancer is one of the most common malignancies in women worldwide, with HER2-positive breast cancer accounting for about 15-20% of all breast cancer cases. HER2 (Human epidermal growth factor receptor 2) is a tyrosine kinase receptor that, when overexpressed, promotes the growth and spread of tumor cells. The advent of anti-HER2 therapy, particularly antibody-coupled drugs (ADCs), has resulted in significant survival benefits for HER2-positive breast cancer subjects. At present, the value of serum HER2 in the monitoring of anti-HER2-ADC drug therapy is insufficient. The purpose of this study was to investigate changes in serum HER2 expression levels in breast cancer subjects treated with anti-HER2-ADC drugs and the relationship between these changes and treatment effect. The therapeutic effect of HER2 was evaluated by continuous detection of HER2 serum, which provided a theoretical basis for the selection of clinical drug treatment.