Company: AZN
Filing Date: 2025-02-28
Form Type: 6-K
Source: 0001654954-25-002102
Chunk: 3

Company: ASTRAZENECA PLC
Filing Date: 2025-02-28
Form: 6-K
Chunk 3
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2-negative. 7

HR-positive, HER2-negative is the most common breast cancer subtype, accounting for approximately 70% of all breast cancers. 4 Endocrine therapies are widely given consecutively in the early lines of treatment for HR-positive metastatic breast cancer. However, after initial treatment, further efficacy from endocrine therapy is often limited. 8 The current standard of care following endocrine therapy is chemotherapy, which is associated with poor response rates and outcomes. 8-11

Despite being classified as HER2-negative, many of these tumours may still carry some level of HER2 expression. 7 In the DESTINY-Breast06 trial, approximately 85-90% of patients with HR-positive, HER2-negative metastatic breast cancer were determined to be HER2-low or HER2-ultralow. 1

Prior to the approval of Enhertu in HER2-low metastatic breast cancer based on the DESTINY-Breast04 trial, there were no targeted therapies specifically approved for patients with HER2-low expression. There are no targeted therapies specifically approved in the EU for patients with HER2-ultralow expression. 12,13

#### DESTINY-Breast06
DESTINY-Breast06 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) versus investigator's choice of chemotherapy (capecitabine, paclitaxel or nab-paclitaxel) in patients with HR-positive, HER2-low (IHC 1+ or 2+/ISH-) or HER2-ultralow (IHC 0 with membrane staining) advanced or metastatic breast cancer. Patients in the trial had no prior chemotherapy for advanced or metastatic disease and received at least two lines of prior endocrine therapy in the metastatic setting. Patients were also eligible if they had received one prior line of endocrine therapy combined with a CDK4/6 inhibitor in the metastatic setting and experienced disease progression within six months of starting 1st-line treatment or received endocrine therapy as an adjuvant treatment and experienced disease recurrence within 24 months.

The primary endpoint is PFS in the HR-positive, HER2-low patient population as measured by blinded independent central review (BICR). Key secondary endpoints include PFS by BICR in the overall trial population (HER2-low and HER2-ultralow), overall survival (OS) in the HER2