ADCs therapy doubles the survival of patients with the “most aggressive breast cancer”

Dato-DXd has now entered the FDA review and evaluation process, and it is expected that the FDA will decide whether to allow it to be marketed in the first quarter of 2025.

⦿ “Difficult” HER2 breast cancer

HER2 breast cancer is also a type of aggressive breast cancer, accounting for 15% to 20% of all breast cancer cases. This type of cancer cell expresses more human epidermal growth factor receptor protein called HER2 on its surface. HER2 breast cancer proliferates and metastasizes faster, so it is more invasive and has a relatively poor prognosis.

HER2 breast cancer is insensitive to traditional chemotherapy, but has a good response rate to ADCs therapy.

1. Trastuzumab Emtansine (T-DM1)

T-DM1 is a second-generation ADCs drug, which was approved by the US FDA in 2013 for the treatment of HER2-positive breast cancer and metastatic breast cancer.

Clinical data show that T-DM1 significantly improves the overall survival rate and disease-free survival of HER2-positive patients, and its side effects are more controllable than traditional chemotherapy. This breakthrough provides a new treatment option for HER2-positive breast cancer patients, especially after early surgery or when traditional treatment is ineffective. T-DM1 has become the standard treatment.

2. Trastuzumab Deruxtecan (Enhertu)

Enhertu is a third-generation ADCs drug approved by the FDA in 2019 for the treatment of unresectable or metastatic HER2-positive breast cancer and HER2-low-expressing breast cancer that have previously received one or more treatments.

In a clinical trial, patients treated with Enhertu had significantly longer progression-free survival and overall survival compared with chemotherapy.

Among all patients, the median progression-free survival was 9.9 months in the Enhertu group and 5.1 months in the chemotherapy group; the overall survival was 23.4 months in the Enhertu group and 16.8 months in the chemotherapy group.

In terms of side effects, 52.6% of patients who received Enhertu experienced adverse events of grade 3 or higher, while 67.4% of patients who received chemotherapy experienced adverse events of grade 3 or higher.