Between one and two in ten cancers are "HER2 positive", where HER2 is the name of a receptor. However, overexposure of this receptor gives cancer cells an advantage. It therefore also represents a therapeutic target of choice. A recent clinical trial demonstrates the interest of a treatment combining a therapeutic antibody and a cytotoxic molecule.
Breast cancer is the deadliest type of cancer in women . In addition, it is the most frequently diagnosed cancer in the world since 2021, a first. Research is continuing, in particular to better detect, diagnose and treat this disease, in particular by means of artificial intelligence.
However, between 10 and 20% of breast cancer cases are HER2+. This means that malignant cells have an abnormal number of HER2 receptors on their surface, which are activated by growth factors. For cancer, this is an undeniable asset, because it allows it to multiply and resist cell death (apoptosis). In addition, malignant cells ensure their supply of oxygen and nutrients with the help of numerous blood vessels.
Although they represent an asset for cancer, HER2 receptors also embody an important therapeutic target . It must be said that the search for overexposure to this receptor is systematic in women with breast cancer. Limiting the growth and multiplication of malignant cells can thus involve blocking the activation of HER2 receptors. This type of breast cancer thus benefits from atwo-level care strategy :the first is a monoclonal antibody that binds to HER2, blocking its activation, the second is a cytotoxic chemical molecule.
Among the combinations available on the market , we find in the first line the monoclonal antibody trastuzumab (Herceptin) and a cytotoxic molecule. In case of disappointing results, trastuzumab is then combined with emtansine, a molecule capable of inhibiting the assembly of microtubules representing a central element of the cytoskeleton. Still in the absence of convincing results, trastuzumab is then combined with deruxtecan. It is a molecule capable of interfering with topoisomerase, an enzyme interacting with DNA.
Published in the New England Journal of Medicine on March 24, 2022, the results of the phase 3 clinical trial Destiny-Breast03 allowed to re-evaluate the trastuzumab-deruxtecan combination . The aim was to determine whether this treatment could be repositioned as a second line, rather than a very last resort, before the trastuzumab-emtansine combination. According to the results, the trastuzumab-deruxtecan treatment allows asignificant increase in survival in female patients.
On 524 participants Randomly divided into two groups, 75% of patients who received trastuzumab-deruxtecane benefited from a progression-free survival of the disease at twelve months. However, this same rate was only 38% in the case of trastuzumab-emtansine, the usual second-choice treatment. In addition, the trastuzumab-deruxtecane combination confers better overall survival.
On the other hand, treatment with trastuzumab-deruxtecane unfortunately causes many side effects . The overwhelming majority of patients observed the onset of lung diseases and infections. Despite this negative point, the trastuzumab-deruxtecane combination actually increases patient survival while reducing the risk of progression HER2+ breast cancer.
