AstraZeneca’s Dato-DXd, an antibody drug conjugate, has shown promising results in a Phase III breast cancer trial, known as TROPION-Breast01, conducted to assess its effectiveness in patients with advanced HR-positive, HER2-low or -negative breast cancer. The trial revealed a significant and clinically meaningful improvement in progression-free survival when compared to chemotherapy chosen by investigators. AstraZeneca intends to share these results with health authorities, indicating a potential breakthrough in breast cancer treatment. The trial involved 733 patients stratified into different groups based on factors such as the number of prior lines of chemotherapy (up to two), prior use of CDK4/6 inhibitors, and geographic region. The primary outcomes measured were progression-free survival and overall survival, while secondary outcomes included the objective response rate, duration of response, and disease control rate. Patients eligible for the trial had HER2-low or -negative breast cancer, determined by HER2 scoring criteria, IHC 0, IHC 1+, or IHC 2+, with a negative FISH result. Additionally, AstraZeneca observed a trend toward improved overall survival with Dato-DXd compared to chemotherapy, although the data were not mature at the interim analysis stage. Importantly, the safety profile of Dato-DXd remained consistent with findings from previous
clinical trials, suggesting that the drug maintains its safety and tolerability. Dato-DXd is an antibody drug conjugate that targets TROP2, jointly developed by AstraZeneca and Daiichi Sankyo. The promising results from this Phase III trial have encouraged further evaluation of Dato-DXd in breast cancer treatment. Two additional Phase III trials, TROPION- Breast02 and TROPION-Breast03, are currently underway. In TROPION-Breast02, the drug is being compared to chemotherapy in patients with previously untreated advanced triple-negative breast cancer, while in TROPION-Breast03, Dato-DXd is being assessed with and without
Imfinzi (durvalumab) compared to the investigator’s choice of therapy in patients with early- stage triple-negative breast cancer and residual disease following neoadjuvant therapy.
These trials are part of AstraZeneca’s broader strategy, announced in July, to replace chemotherapy in late-line breast cancer treatment across all disease subtypes with targeted therapies, including Enhertu (trastuzumab deruxtecan) and Dato-DXd. This approach reflects the growing emphasis on personalized and targeted treatments in the fight against breast cancer, potentially offering improved outcomes and fewer side effects for patients. The positive outcomes from TROPION-Breast01 represent a significant step forward in realizing this strategy’s potential to revolutionize breast cancer treatment.
