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Breast cancer, new targeted therapies to improve control of the disease

The ECHO that reaches from San Antonio, Texas, where a few weeks ago was held at the world congress on breast cancer, it brings important news. Especially for t

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Breast cancer, new targeted therapies to improve control of the disease
The ECHO that reaches from San Antonio, Texas, where a few weeks ago was held at the world congress on breast cancer, it brings important news. Especially for those who have a type of cancer defined HER2 - positive, advanced-stage. To make the point on the studies presented in the United States is the national conference Back from San Antonio, which opens today in Genoa, an event now in its thirteenth edition.

“In some types of breast cancer, which account for between 15% and 20% of all cases, a protein, HER2, is present in excessive amounts, causing rapid and uncontrollable growth of the diseased cells,” explains Lucia Del Mastro, Head of the Breast Unit of the Policlinico-IRCCS Hospital San Martino and the president of the conference: “From biological point of view, is one of the most aggressive forms, and, in the past, since there is no available weapons, the patients with cancer had the worse prognosis. Today, however, thanks to targeted therapies that block the HER2 receptor, their clinical course is dramatically changed”. And the prospects continue to improve: “there Are three studies more interesting presented Congress San Antonio, all of them involve this form of breast carcinoma and are likely to determine a further improvement of the prognosis,” continues The Master.
The drug is effective in those who have already received a lot of treatments The first study concerns a new drug, trastuzumab deruxtecan, an antibody - conjugate, i.e. a molecule that arises from the union of a monoclonal antibody (trastuzumab) with chemotherapy (deruxtecan): “it Is a therapy which is very powerful, that is able to send 8 molecules of chemotherapy for each antibody, by acting not only on the tumor cell that is the target, but also on those nearby,” explains the oncologist. The study presented - and published simultaneously in the New England Journal of Medicine, involved 184 patients already very treated: they had previously received from 2 to 27 treatments (six in average). In spite of this, the objective response rate (where there is observed a regression of the tumor), has exceeded 60%. In 97.3% of cases the disease is not progressed, with a median progression-free survival of 16 months. “It is - highlights Of the Master - a clinical result ever observed in a subset of patients heavily pre-treated, that has exhausted all standard therapies”. For the relevance of these data, the 24 December, the Food and Drug Administration, the agency that the regulatory united states, has approved the molecule, although the study (called Destiny-Breast01) was phase II. “Currently the drug is in testing in phase III studies and to be studied in depth its possible use also in those that have a low expression of the HER2 protein, and in which, to date, there is no indication to receive a treatment targeted against the protein”. In Europe and in Italy, currently the medication is not available if you are not within the clinical trials. In Genoa, in particular, are two on-going testing: a comparison with the current standard of care, the TDM-1 is another antibody conjugate trastuzumab emtansine) and in patients in which the TDM-1 has failed. Every year in the San Martino hospital, more than 2 thousand patients become part of clinical trials.
The molecule that slows the metastasis of the brain The second innovation concerns tucatinib, an inhibitor of an oral HER2 that has shown to be effective against brain metastases, present in about half of the cases in this population of patients. Even this study, which involved more than 600 women who had already previously received an average of three treatments, was published in the New England Journal of Medicine. “The addition of tucatinib of standard therapy with capecitabine and trastuzumab, has resulted in an increase in both progression-free survival and the overall survival: in two years he was alive, 45% compared to 27% of the control arm,” explains The Master: “Not only that: at a distance of a year, the disease control at the brain level has been observed in 25% of cases treated with tucatinib compared to 0% of cases treated with the standard therapy”. The medication could then be used for the prevention of this type of metastasis.
New data for those who are at greatest risk of recurrence, The third study presented in San Antonio is always about the patients with tumor HER2-positive, but in the initial stage. This is an update of the study of the phase III Aphinity, which has evaluated a molecular-targeted drug, pertuzumab in addition to trastuzumab and chemotherapy as adjuvant treatment (i.e. after surgery to reduce the risk of recurrence of the disease). “At a median follow up of approximately 6 years – says The Master – the greatest benefit was observed in patients at high risk of recurrence, that is, with positive axillary lymph nodes. With the regime at the base of pertuzumab was obtained a 28% reduction in the risk of recurrence or death compared with trastuzumab, chemotherapy and placebo. This corresponds to an absolute improvement of the increase of disease-free survival at six years of 4.5%, in this population of patients is clinically significant”.
Confirmations for the inhibitors of CDK4/6 By the United States arrive, finally, confirmation of the effectiveness of the new treatments also for those who have a cancer positive for hormonal receptors and HER2 negative (HR+/HER2-), in postmenopausal women with metastatic disease. “This subtype includes about 65% of all metastatic cases, says Carmine De Angelis, a researcher from the University of Naples Federico II and Professor of the Baylor College of Medicine in Houston and among the speakers at the convention in San Antonio: “it Is shown that the combination of hormone therapy and new molecular-targeted therapy (inhibitors of CDK4/6) is better with respect to only the hormonal therapy standard: progression-free survival is doubled. Not only. No chemotherapy regimen has proved more effective than the combination. In these patients, the clinical practice is progressively moving away from the use of chemotherapy for the adoption of the combination, first-line, several molecules of a molecular target with endocrine therapy”.

Currently, about 10% of new diagnoses and is already metastatic. “In these cases, a time, there were few options, today, thanks to research, it is not more so,” says The Master: “The metastatic breast cancer is a disease that, in many cases, it is possible to keep under control for very long periods, results that were unthinkable only a decade ago. We have several weapons available, from chemotherapy to hormone therapy to molecules of a molecular target, up to immunotherapy”.

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