Ieo, Conjugated Antibodies Breakthrough Against Metastatic Breast Cancer

A breakthrough against metastatic breast cancer. This is how the European Institute of Oncology (IEO) in Milan presents the results of an international study coordinated by Giuseppe Curigliano, director of the Division of New Drugs for Innovative Therapies at the IEO and president-elect of ESMO (European Society of Medical Oncology), “destined to change clinical practice in the treatment of metastases of the most common breast tumors”, those positive for hormone receptors (Hr+), which represent 70% of the total. The authors of the study – published in the ‘New England Journal of Medicine’ – have in fact demonstrated that for this type of neoplasm “the use of the conjugated antibody trastuzumab deruxtecan after standard hormone therapy for the initial phases improves progression-free survival” of the disease, “compared to chemotherapy, and reduces the overall risk of progression and death. Trastuzumab deruxtecan is confirmed as a new treatment option, between endocrine therapy and chemotherapy, capable of increasing the disease-free period by an average of 5 months”.

“This study – says Curigliano – is a milestone towards the definition of effective therapies for metastatic estrogen receptor-positive (Er+) breast cancers with low levels of expression of the Her2 receptor (Her2 low). For patients it is a turning point because the word ‘metastasis’ itself will be less scary and they will adhere to treatment with more confidence. With the right sequence of therapies, the chronicization of metastatic disease is now an achievable goal”.

Currently – recalls a note from the IRCCS founded by Umberto Veronesi – after endocrine therapy in the initial stages, the standard of care is chemotherapy, whose benefits are notoriously not satisfactory. The possibility of a turning point arose a few years ago from conjugated antibodies, new targeted drugs composed of an antibody capable of recognizing the receptors for Her2, conjugated to chemotherapy molecules. In essence, the antibody recognizes the receptors, penetrates the tumor cell and releases the destructive charge of the chemotherapy, acting like a Trojan horse. One of these drugs is trastuzumab deruxtecan, a molecule capable of binding to Her2 receptors, even if only weakly expressed by the tumor cell. The drug is already used in metastatic breast cancer, but as a second line of treatment, after chemotherapy. In the study just published (Destiny-Breast06), the authors evaluated the use of the conjugated antibody immediately after endocrine therapy, avoiding chemotherapy treatment.

“The results were extraordinary”, assure the IEO. “In the study – highlights Curigliano – patients with metastatic breast cancer Hr+, Her2 low and Her2 ultralow treated with trastuzumab deruxtecan after endocrine therapy lived longer (on average 5 months more) without progression or worsening of the disease, compared to those treated with standard chemotherapy”.

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“This result – concludes the specialist – changes the way of treating Hr+ metastatic breast cancer, because by using trastuzumab-deruxtecan earlier we not only obtain a more effective treatment, but we can extend the population of patients who can benefit from it”.