“We are probably looking at the most relevant, important and impactful results in the history of breast cancer”, states Dr. Javier Cortés, director of the International Breast Cancer Center (IBCC), referring to the results of Destiny Breast-03. Dr. Cortés, who led this study and is its leading author, has presented his results for the first time at the Presidential Symposium of the ESMO Congress 2021.
The Destiny Breast-03 study has shown that trastuzumab deruxtecan acts as ‘Trojan horse’ drug and it is highly effective against HER2-positive metastatic breast cancer as a second-line treatment. Trastuzumab deruxtecan is a antibody-drug conjugate, which includes immunotherapy (trastuzumab), a monoclonal antibody directed against the HER2 receptor, coupled with an effective chemotherapy (deruxtecan) which is a derivative of exatecan, a potent inhibitor of topoisomerase I. The antibody is able to enter tumour cells and ‘trick’ them because they do not detect the chemotherapy. Once inside, the antibody releases the chemotherapy, previously undetected by the cancer cells, and this exerts a powerful activity that destroys them from within, while leaving healthy tissue undamaged.
HER2-positive breast cancer accounts for around 15-20% of all breast cancer cases and is a subtype characterized by high aggressiveness and high proliferative capacity. Although there are already other drugs that work against targets, in this case the HER2 receptor, and other approved “trojan horses”, trastuzumab deruxtecan has shown the most striking activity so far, according to the results of the Destiny Breast-03 study.
“Of all the studies of breast cancer, at all stages, at all times, in all of the subtypes, there has never been a drug that has shown as much benefit as this one has. That’s not my opinion. It’s objective data. I think it is the most relevant, most important and most impactful data in the history of breast cancer”, says Dr. Javier Cortés.
Results of ‘Destiny Breast-03’
Destiny Breast-03 is a randomized, multicentre, phase III clinical trial that included 524 patients previously treated with a line of chemotherapy treatment called taxanes and with trastuzumab. Participating patients were randomly assigned (1:1) to one of the two study arms: 261 to the trastuzumab deruxtecan arm and 263 to the T-DM1 standard treatment arm. The primary objective of the study was to analyze progression-free survival (PFS). For this indicator, 75.8% of patients treated with traztuzumab deruxtecan in the second line remained without progression or worsening of the disease at 12 months, compared to 34.1% of patients treated with T-DM1. This is a statistically and clinically significant improvement on the current standard treatment.
It is also worthy of note that, after this 12-month analysis, median progression-free survival has not yet been reached in patients treated with trastuzumab deruxtecan. According to Dr. Cortés, “more than 50% of patients remain without metastatic disease getting worse at 24 months”.
The other fundamental secondary objective of this clinical trial was overall survival. For this indicator, treatment with trastuzumab deruxtecan has also shown a strong trend towards improved overall survival, although the data from this study is not yet conclusive.
The safety profile of trastuzumab deruxtecan is consistent with that observed in previous clinical trials, with no new safety concerns becoming evident. “The toxicity is manageable, although 1 in 10 patients may develop pneumonitis or inflammation of the lungs. It’s very important to know that this toxicity can occur and know how to handle it properly. If handled well and promptly, it is a toxicity that will not cause problems. But we must work together to diagnose it in time so that it’s manageable and doesn’t impact on patients’ quality of life”, stresses Dr. Cortés, who says that quality-of-life studies are being carried out with favourable preliminary results.
For the time being, the results of Destiny Breast-03 position trastuzumab as the second-line treatment of choice for patients with HER2-positive metastatic breast cancer. This drug had already been pre-approved by regulatory agencies, pending endorsement following the presentation of a phase III study, such as Destiny Breast 03, which has now taken place this weekend at the ESMO Congress 2021. Given these results, “we assume that the European Medicines Agency (EMA) will soon carry out a modification of the current data sheet of trastuzumab deruxtecan and will allow its use in patients who have previously received a line of treatment”, reveals Dr. Cortés.