Company: AZN
Filing Date: 2025-02-26
Form Type: 6-K
Source: 0001654954-25-001920
Chunk: 2

Company: ASTRAZENECA PLC
Filing Date: 2025-02-26
Form: 6-K
Chunk 2
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 in three patients with HR-positive, HER2-negative advanced breast cancer whose tumours develop ESR1 mutations during treatment with an aromatase inhibitor in combination with a CDK4/6 inhibitor. This critical read-out moves us one step closer to realising the potential of camizestrant to become a new standard-of-care as we look to shift the treatment paradigm and establish this new endocrine therapy backbone in HR-positive breast cancer."

The safety profile of camizestrant in combination with palbociclib, ribociclib or abemaciclib in SERENA-6 was consistent with the known safety profile of each medicine. No new safety concerns were identified and discontinuations were very low and similar in both arms.

Globally, approximately 200,000 patients with HR-positive breast cancer are treated with a medicine in the 1st-line setting; most frequently with endocrine therapies that target estrogen receptor (ER)-driven disease, which are often paired with CDK4/6 inhibitors. 1-3However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease. 3

Mutations in the ESR1gene are a key driver of endocrine resistance and are widely tested for in clinical practice. 4,5These mutations develop during treatment of the disease, becoming more prevalent as the disease progresses and are associated with poor outcomes. 4,5Approximately 30% of patients with endocrine sensitive HR-positive disease develop ESR1mutations during 1st-line treatment without disease progression. 1

Data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

#### Notes

#### HR-positive breast cancer
Breast cancer is the second most common cancer and one of the leading causes of cancer-related deaths worldwide. 6More than two million patients were diagnosed with breast cancer in 2022, with more than 665,000 deaths globally. 6While survival rates are high for those diagnosed with early breast cancer, only about 30% of patients diagnosed with or who progress to metastatic disease are expected to live five years following diagnosis. 7

HR-positive breast cancer, characterised by the expression of estrogen or progesterone receptors, or both, is the most common subtype of breast cancer with 70% of tumours considered HR-positive and HER2-negative. 7ERs often drive the growth of HR-positive breast cancer cells. 8

Once resistance to the treatment of HR-positive breast cancer with