There are good news in the fight against breast carcinoma. Trastuzumab deruxtecan, a new drug, stops the progression of advanced HER2-positive metastatic cancer (T-Dxd), which is a highly aggressive form of breast cancer that affects 20%. This breakthrough was made in the framework of international clinical trial Destiny Breast-03, which Javier Cortes from Madrid, the International Breast Cancer Center’s (IBCC), and the sole Spanish author of this study, has led.
An immunoconjugate is a new drug that contains chemotherapy molecules. It is an antibody that is secreted in the blood by B lymphocytes to fight infection by bacteria or viruses that can affect the body. His behavior is similar to that of a trojan horse. It travels through the bloodstream to cancer cells that possess a receptor called “HER2”. The drug travels through the blood to tumor cells that have HER2. Once inside, it releases chemotherapy and transports it away. Cortes explains that this drug is still in the tumor microenvironment. It can also attack neighboring cells even if they don’t have HER2. This is called the “bystander effect” or the ‘bystander impact’.
The trial included 524 women with HER2-positive metastatic cancer. They were recruited at 169 centers across 15 countries between 2018 and 2020. From these 524 women, 261 were randomly assigned into the T-Dxd arm and 263 to TDM-1 arm. This was the standard treatment until publication of this research in The New England Journal of Medicine.
The ‘Trojan Horse” against breast cancer
Trastuzumab desuxtecan (T–Dxd), acts as a Trojan horse because it enters the tumor cells undetected and releases the chemotherapy.
One
Stream
Sanitation
T-Dxd
immunoconjugate drug
(chemomolecules
Monoclonal antibody
HER2
protein against
The one who acts
Drug and door
Entrance to the
Tumor cell
Cancer cell
2
The drug is absorbed into the body.
The tumor cell is not being
Detected
3
T-Dxd allows for the release of chemotherapy
The nucleus of a cell
Core
DNA
Infected
4
T-Dxd, the drug that was released, could also attack neighboring cancer cells. This is a very positive and novel approach to breast cancer drugs, even though it may cause some damage to healthy cells.
The tumor cell is dead
SOURCE: IBCC
The ‘Trojan Horse” against breast cancer
Trastuzumab desuxtecan (T–Dxd), acts as a Trojan horse because it enters the tumor cells undetected and releases the chemotherapy.
One
2
Stream
Sanitation
The drug is absorbed into the tumor cells without being detected.
Detected
T-Dxd
immunoconjugate drug
(chemomolecules
Monoclonal antibody
HER2
The drug works against the protein and the gateway to the cancer cell
Cancer cell
3
4
T-Dxd allows for the release of chemotherapy
The nucleus of a cell
T-Dxd, the drug that was released, could also attack neighboring cancer cells. This is a very positive and novel approach to breast cancer drugs, even though it may cause some damage to healthy cells.
Core
DNA
Infected
The tumor cell is dead
SOURCE: IBCC
The study’s most significant result was the increase in progression-free survival, or disease control, after 12 months. This figure was 75.8% for patients who received TDM-1, and 34.1% for those who received TDM-1. T-Dxd’s efficacy was also demonstrated in 42 patients (16.1%), compared with 23 (8.7%) who received TDM-1.
“Out of all the breast cancer research, this drug has been shown to be as effective as any other. This could be the most effective drug ever developed for breast cancer. These are the most important, relevant and impressive data I have seen to date,” Dr. Cortes says. He predicts that T-Dxd could eventually cure some patients, or at the very least increase their chances of being chronic.
Trastuzumab deuxtecan is now the standard second-line treatment for patients with HER2-positive metastatic cancer. It is used when other treatments fail or are no longer effective. The research also shows that it is being used in breast cancers that express low levels of HER2. This represents 55% of all breast cancers. He says that the first randomized trial in this patient group will be published in June. However, the results so far have been extremely positive. Its administration is also being studied to combat other types of cancer that have the HER2 protein. There are already published data about colorectal, lung and gastric cancer.
It is possible to get toxicity from it, as with all treatments. Drug-related interstitial pulmonary disease/pneumonitis (lung swelling) is one of the side effects. T-Dxd had a 10.5% rate of interstitial lung disease/pneumonitis compared to 1.9% for TDM-1. However, close monitoring and follow-up of patients who have been treated with TDM-1 allows early detection and treatment of the adverse effect and management of it in most patients.
Although the drug has been approved for use in Spain, negotiations regarding its price have not been concluded with the Ministry of Health. We are in the midst of a revolution. These “Trojan horses” will be one of the most important research areas in the future. Cortes says that there are studies already showing amazing results.
