From Berlin, where the Esmo Breast – the European congress of medical oncology entirely dedicated to breast cancer – was held last week, comes the echo of three words: conjugated monoclonal antibodies. A difficult name that however carries with it a simple concept: that of the Trojan horse. In fact, just like in the myth of the Aeneid, these drugs bring chemotherapy directly into the cancer cell. And they are producing important results against breast cancer.
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“The most important studies presented at Esmo Breast concerned the role of conjugated antibodies, in particular for HER2 positive tumors, which represent about one fifth of all breast cancers”, confirms Giuseppe CuriglianoHead of the New Drugs Development Division at the European Institute of Oncology and Full Professor of Medical Oncology at the University of Milan: “The data on the quality of life of metastatic patients treated with trastuzumab deruxtecan in the Destiny-Breast03 study are worth mentioning. Great surprise of the researchers, the drug not only preserved it, but even improved some variables. In particular, pain control, time to hospitalization and the emotional perception of the quality of life itself, which is extremely important and indicative ” .
One antibody for 8 ‘bullets’
Trastuzumab deruxtecan arises from the union of a monoclonal antibody – trastuzumab – with the particularly powerful chemotherapy deruxtecan. Each molecule of trastuzumab binds to itself 8 molecules of deruxtecan. The mechanism by which it acts, simplifying, is this: trastuzumab recognizes and binds to the HER2 receptors present on the tumor cell and, at that point, releases the 8 “bullets” (ie molecules) of the chemotherapy into it. Just like a Trojan horse. The first important data on this drug dates back to December 2019, when at the breast cancer congress in San Antonio, Texas, the Destiny-Breast03 study demonstrated significant advantages over TDM-1 (trastuzumab emtansine, the current standard of care for patients with HER 2 positive tumors), for patients who had previously received many treatments (2 to 27).
San Antonio Breast Cancer Symposium: the news from the great American congress dedicated to breast cancer
by MARIA TERESA BRADASCIO
20 December 2019
Triples survival
Even on the basis of subsequent data, the drug has been shown to triple median survival and reduce the risk of disease progression by 72%. “This is an impressive advantage in disease control, far above the standard of care, but the data on the quality of life, which has now arrived, was still lacking,” Curigliano points out. Another study, Tuxedo-1 (phase II), also presented at Esmo Breast, has also shown that conjugated antibodies can also be active on brain metastases. 15 patients treated with trastuzumab deruxtecan were involved: the response in non-pretreated brain metastases was high, 73% (11 patients) with 14 months of progression-free survival, which means that the therapeutic effect of these drugs on the nervous system are there and will need to be investigated further.
Esmo 2021
Metastatic breast cancer, monoclonal antibody triples survival
by Irma D’Aria
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More studies are needed
The drug has been approved in Europe since the end of 2020 for patients with metastatic HER2-positive cancer who have already received two or more HER2 therapies, i.e. from the third line of treatment onwards (in Italy it has been approved for over a year, but in the Cnn, therefore not yet refundable). In the US – it is news these days – its use has been brought forward to the second line (ie after only one other anti-HER2 therapy). Not only that: the FDA has just designated it as “Breakthrough Therapy” for the so-called HER2 Low breast tumors, which express low levels of the HER2 receptor: it means that the approval also for these patients will be speeded up. “It seems that this drug gives an advantage in terms of disease control and overall survival for this group of patients, but to see the data that led the FDA to this decision we will have to wait for the Asco congress, in a few weeks” , says Curigliano.
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by Viola Rita, Tiziana Moriconi
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High-risk early breast cancer
Returning to Esmo Breast, other important findings concerned the most common initial breast cancer (the one sensitive to female hormones, which represents 60-70% of all cases) in women at high risk of recurrence and metastasis. In the update of the MonarchE study (which we have already told you about in the Health Breast newsletter), the targeted drug abemaciclib used as adjuvant therapy (after surgery) together with standard endocrine therapy has shown significant benefits in both young and female women. less young, that is, regardless of whether or not they were in menopause. Three years after the start of the study, the percentage of women without the disease was 89.5% for those who had also received abemaciclib compared to 83% for those who had only received standard endocrine therapy; the percentages of metastasis-free patients were 90.5% and 86%, respectively. Abemaciclib is the first (and currently only) anti-CDK 4/6 approved as an adjuvant therapy in Europe.
The next important appointment with research, we said, will be held from 2 to 7 June, when the eyes of the world of oncology – including ours – will be on Chicago.
San Antonio Breast Cancer Symposium: the news from the great American congress dedicated to breast cancer
by MARIA TERESA BRADASCIO
20 December 2019