AstraZeneca and Daiichi Sankyo Secure FDA Approval for Enhertu Label Expansion in Breast Cancer

In a significant development for breast cancer treatment, AstraZeneca and Daiichi Sankyo have received FDA approval for a label expansion of their antibody-drug conjugate (ADC) Enhertu (fam-trastuzumab deruxtecan-nxki). This expansion broadens the drug's application to include patients with unresectable or metastatic breast cancer who are HR-positive and HER2-low or HER2-ultralow, marking a notable advancement in targeted therapies for this patient population.

Expanded Indications and Clinical Impact

The FDA's decision, announced on January 28, 2025, positions Enhertu as the first HER2-directed therapy approved for HER2-low and HER2-ultralow metastatic breast cancer in patients whose disease has progressed after at least one prior line of endocrine therapy. This approval significantly expands the potential patient population that can benefit from Enhertu, bringing it to an earlier treatment setting.

Dave Fredrickson, executive vice president of AstraZeneca's Oncology Hematology Business Unit, emphasized the importance of this development, stating that it will bring Enhertu "to an earlier treatment setting and a broader patient population with HER2 expressing metastatic breast cancer."

Clinical Trial Results and Efficacy Data

The label expansion was supported by data from the Phase III DESTINY-Breast06 trial, which demonstrated Enhertu's superior efficacy compared to chemotherapy in the target patient group. Key findings from the trial include:

• A 36% reduction in the risk of disease progression or death compared to chemotherapy
• A confirmed objective response rate (ORR) of 62.6% for Enhertu, versus 34.4% for chemotherapy
• An exploratory analysis showing a 24% improvement in progression-free survival for patients with HER2-ultralow disease, although this did not reach statistical significance

Safety Considerations and Adverse Events

While Enhertu demonstrated overall tolerability, the trial data revealed important safety considerations:

• 20% of treated patients developed serious adverse events
• Common serious toxicities included interstitial lung disease (ILD), hypokalemia, and febrile neutropenia
• 2.8% of patients experienced treatment-related adverse events leading to death
• Enhertu's label carries a boxed warning for ILD and embryo-fetal toxicity

These safety findings underscore the need for careful patient monitoring and management during Enhertu treatment.