The U.S. FDA has approved capivasertib in combination with Faslodex for the treatment of patients wi

On November 17, 2023, AstraZeneca’s capivasertib in combination with Faslodex (fulvestrant) was approved in the United States for the treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer, who harbor one or more biomarker alterations (PIK3CA, AKT1, or PTEN). Eligible patients must have experienced disease progression following at least one endocrine-based therapy regimen in the metastatic setting, or have relapsed during or within 12 months of completing adjuvant therapy.

This approval by the U.S. Food and Drug Administration (FDA) was based on results from the phase III CAPItello-291 trial, published earlier this year in The New England Journal of Medicine. In the trial, among patients whose tumors had PI3K/AKT pathway biomarker alterations, capivasertib (Truqap) in combination with Faslodex reduced the risk of disease progression or death by 50% compared with Faslodex alone (based on a hazard ratio of 0.50; 95% confidence interval [CI], 0.38–0.65; p<0.001; median progression-free survival [PFS] was 7.3 months versus 3.1 months, respectively).

Breast cancer is the most common cancer worldwide and one of the leading causes of cancer-related deaths. HR-positive breast cancer (expressing estrogen receptor, progesterone receptor, or both) is the most prevalent subtype, accounting for over 65% of all breast tumors that are classified as HR-positive with either low HER2 expression or HER2 negativity. Overall, genetic alterations in PIK3CA, AKT1, and PTEN are frequently observed, affecting up to 50% of patients with advanced HR-positive breast cancer. Endocrine therapy is widely used in this patient population, but many patients develop resistance to first-line cyclin-dependent kinase 4/6 (CDK4/6) inhibitors and estrogen receptor-targeted therapies, highlighting an urgent need for additional endocrine-based treatment options.

Dr. Komal Jhaveri, a medical oncologist at Memorial Sloan Kettering Cancer Center in the United States, stated: "Patients with advanced HR-positive breast cancer typically experience tumor progression or develop resistance after receiving widely used first-line endocrine therapies, and there is an urgent need to extend the effectiveness of these treatments. Capivasertib in combination with fulvestrant, this first-in-class regimen, provides a much-needed new treatment option for the subset of patients—up to half of this population—who harbor these specific biomarkers, with the potential to delay disease progression and achieve longer periods of disease control."