Researchers from the Hospital Clínic-IDIBAPS, the Catalan Institute of Oncology (ICO) and the Vall d'Hebron Institute of Oncology (VHIO) have participated in an international study that demonstrates the efficacy of a new drug for metastatic breast cancer with a low HER2 expression. The treatment manages to double survival without disease progression in patients with this type of tumor, compared to standard treatments.
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The breast cancer It is the most common tumor in women worldwide, affecting 2.3 million people and causing the death of 571,000 each year. The molecular classification of breast cancer makes it possible to decide which is the best treatment based on the characteristics of the tumour. Among the various subtypes, HER2-negative breast cancers account for 70% of all tumors.
Levels of HER2, a protein found on the outside of tumor cells, are routinely measured to decide the appropriate treatment strategy for breast cancer. In the case of HER2-negative metastatic tumors, it has been seen that 55% do not have amplification of the HER2 gene (therefore, until now they are considered HER2-negative), but 70% of these express low levels of the HER2 protein (HER2-low).
These HER2-low tumors are a very heterogeneous group that includes two other subtypes depending on whether or not the tumor cells express hormone receptors (HR): HR positive or HR negative.
"Until now, patients with HER2-negative tumors did not benefit from anti-HER2 treatments such as trastuzumab, an antibody that has changed the course of HER2-positive breast cancer," explains Dr. Aleix Prat, member of the steering committee responsible for the clinical trial. "Now, thanks to this new immunoconjugate drug, which combines 7-8 molecules of a very powerful chemotherapy with the antibody trastuzumab, the survival of patients is prolonged," he adds.
Trastuzumab deruxtecan is a new drug that conjugates a monoclonal antibody (trastuzumab) with a chemotherapy agent (deruxtecan) and has recently been approved for the treatment of HER2+ metastatic breast cancer by the United States and European Medicines Agency. Now, this drug can also target tumor cells that express low levels of HER2 and transport the cytotoxic load to these tumor cells but also to neighboring cells without HER2 expression, an effect known as “bystander”.
“One of the current challenges will be to ensure that HER2 levels are adequately monitored; until now it was not important, but now it is very important, and previous studies show great disagreement between pathologists to identify low levels of HER2”, explains Dr. Maria Vidal.
The conclusions of the study
The study published in New England Journal of Medicine (NEJM) has evaluated the use of this drug against the specialist's choice treatment in patients with HER2-low breast cancer who had received one or two previous chemotherapy treatments in addition to hormonal treatment. The trial involved 557 patients, of whom about 90% had a HR-positive tumor and 10% had a HR-negative tumor.
Progression-free survival was about 10 months when trastuzumab deruxtecan was used and 5.1 months with standard chemotherapy. Median survival was 23.4 months compared to about 17 months for the same comparison.
“The results obtained are statistically significant, clinically very relevant and with very manageable adverse effects. This treatment will soon become a standard, and we hope that it will not take long for it to be incorporated into the public system once it is approved by the European Medicines Agency and the Spanish Agency for Medicines and Health Products”, comments Dr. Miguel Gil.
Thus, the research concludes that treatment with trastuzumab deruxtecan is the first therapy directed against HER2 that demonstrates a significant clinical benefit in patients with metastatic breast cancer with low expression of HER2 (HER2-low).
"The drug continues to be evaluated in earlier phases of the disease, when patients have not yet received chemotherapy for their metastatic disease, to see if it improves efficacy even more, as well as in patients with tumors that have minimal expression of HER2 and no were included in this first study”, concludes Dr. Cristina Saura, who has participated in the article.