The latest results from the Destiny-Breast03 study presented by Spanish oncologist Javier Cortés at the 2024 Annual Meeting of the American Society of Clinical Oncology (ASCO) show that Trastuzumab deruxtecan (T-Dxd) delays the progression of metastatic or HER2+ breast cancer. non-operable and achieves the greatest increase in survival in patients with the disease. Specifically, 67% of patients with this type of cancer – which represents around 15% of breast cancers and is one of the most aggressive – are alive after three years of treatment.
Trastuzumab deruxtecan (T-DXd) acts as a ‘Trojan horse’ because it is designed to deceive the “enemy defenses”, penetrate the “cellular walls” and, once inside, unleash its “soldiers” to fight against the tumor from within, reported the IBCC-International Breast Cancer Center-Pangaea Oncology of Barcelona. The study has been published in Nature medicine.
This drug is composed of an antibody or protein (trastuzumab) that includes a type of hidden chemotherapy (deruxtecan) that tumor cells are not able to detect. The antibody binds to a kind of antenna, the HER2 receptor – which is located in the membrane of cancer cells – which enters these cells and releases the chemotherapy inside them to destroy them from within.
The effectiveness of this medication had already been previously observed in other studies and, in fact, its use is approved in countries such as the United States, where it is indicated for patients with this advanced tumor subtype who have not responded to previous treatment or have experienced a recurrence of the disease.
An effective and safe treatment for metastatic breast cancer
Trastuzumab deruxtecan (T-DXd) showed significantly improved efficacy compared to trastuzumab emtansine (T-DM1) in the DESTINY-Breast03 study (mean follow-up 28 months). Patients with advanced HER2-positive metastatic breast cancer, previously treated with taxanes and trastuzumab, were randomly assigned to receive T-DXd (5.4 mg per kg, 261 patients) or T-DM1 (3.6 mg per kg, 263 patients).
The primary endpoint was progression-free survival (PFS). The key secondary endpoint was overall survival (OS). Other secondary objectives included objective response rate, duration of response, and PFS (all assessed by the investigators), as well as safety.
Trastuzumab deruxtecan is designed to enter cancer cells and, once inside, release its “soldiers” to fight the tumor from within.
Using data as of November 20, 2023, median progression-free survival was 29 months in the T-Dxd group versus 7.2 months in the T-DM1 group. The 36-month PFS rate was 45.7% vs 12.4%, and the median overall survival was 52.6 vs 42.7 months with T-DXd compared with T-DM1, respectively. and with a reduction in the risk of death of around 27%, something that had not been previously observed in patients with breast cancer at this advanced stage.
This long-term analysis reinforces the superiority of T-DXd over T-DM1 in patients with metastatic breast cancer previously treated with taxane and trastuzumab, with the longest median overall survival reported in this disease setting and more than two-thirds ( 67.6%) of patients are still alive at 3 years. The clinically significant improvement in efficacy was consistent with the previous data limit. The safety profile of T-DXd remains manageable and no cumulative toxicities are observed with longer follow-up, the researchers conclude in their paper.
