A new treatment against breast cancer with low HER2 expression could be authorized soon after its effectiveness in this type of tumor has been proven. This is Enhertu (trastuzumab deruxtecan), from Daiichi Sankyo and AstraZeneca, which in an international trial has managed to double survival in patients with this type of tumor compared to standard treatments.
Experts from the Hospital Clínic-IDIBAPS, the Catalan Institute of Oncology (ICO) and the Vall d’Hebron Institute of Oncology (VHIO) have participated in the research, which has been published in The New England Journal of Medicine (NEJM). The results have been presented at the American Congress of Oncology (ASCO 2022).
To better understand the importance of this work, it is necessary to know that HER2 is a protein that determines the type of treatment that is going to be administered. When it is highly expressed in the tumor, the cancer is said to be HER2-positive, and if its expression is low, it is said to be HER2-negative, the latter representing 70% of all breast cancers. However, researchers have observed that there are tumors that, although they are HER2-negative, have some HER2 expression, which are known as HER2-low.
Thus, the study has shown that a drug against this protein is not only effective in positive ones, which represent 20% of all breast cancers, but also acts against HER2-low tumors, which are a 50% of the total. In this way the number of patients who could benefit from these treatments could increase to 30%.
The union of a monoclonal antibody and a chemotherapeutic
“Until now, patients with HER2-negative tumors did not benefit from treatments against HER2 such as trastuzumab, an antibody that has changed the evolution of HER2-positive breast cancer”, explained Aleix Prat, one of the researchers of the work .
Specifically, evidence has been found stating that the combination of the drug trastuzumab, which is a monoclonal antibody, and deruxtecan, a chemotherapy agent, achieved progression-free survival and doubled survival in patients with HER2-low breast cancer.
Trastuzumab deruxtecan was able to increase progression-free HER2 breast cancer survival to 10 months compared to 5 months with chemotherapy
The results of the study, which was done in 557 patients, achieved a progression-free survival of about 10.1 months in all those who took trastuzumab deruxtecan, compared to 5.4 months with conventional chemotherapy. Median overall survival was 23.9 months versus about 17.5 months for the same comparison.
There was also a 49% reduction in the risk of cancer progression and a 36% reduction in the risk of death compared to those who received standard chemotherapy treatment.
This would indicate that trastuzumab deruxtecan – which combines 7 or 8 molecules of a very powerful chemotherapy – is much more effective than conventional chemotherapy in people with breast cancer with low levels of HER2 who have already received treatment before. Thus, it could also target tumor cells that express low levels of HER2 and that transport the cytotoxic load to these tumor cells and to neighboring cells without HER2 expression; this effect is known as bystander.
The adverse events of this new treatment are similar to those observed in chemotherapy treatments, although an increase in pulmonary toxicity was found, an important safety problem that should be closely monitored.
“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”, concludes Miguel Gil, oncologist of the ICO and another of the authors of the study.
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