AstraZeneca (AZ) has announced positive high-level results from two individual advanced breast cancer trials evaluating both its next-generation oral selective oestrogen receptor degrader (ngSERD) camizestrant, and capivasertib in combination with Faslodex (fulvestrant).
CAPItello-291 is a phase 3, double-blind trial evaluating the efficacy of capivasertib in combination with Faslodex versus placebo plus Faslodex in patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-low or negative locally advanced or metastatic breast cancer, following recurrence or progression on or after endocrine therapy (with or without a CDK4/6 inhibitor).
SERENA-2 is a randomised, open-label, parallel group, multicentre phase 2 trial evaluating camizestrant at 75mg and 150mg dose levels compared to Faslodex 500mg in post-menopausal patients with oestrogen receptor (ER)-positive, locally advanced or metastatic breast cancer, previously treated with endocrine therapy for advanced disease.
Both trials met their shared primary endpoint of demonstrating a statistically significant and clinically meaningful progression-free survival (PFS) benefit with the respective treatments under evaluation. Additionally, CAPItello-291 met a second primary endpoint, improving PFS in a prespecified biomarker subgroup of patients whose tumours had qualifying alterations in the PIK3CA, AKT1 or PTEN genes.
In terms of safety, both treatments were well tolerated and their safety profiles consistent with that observed in previous trials.
Breast cancer is the most common cancer worldwide, with an estimated 2.3 million patients diagnosed in 2020. HR-positive breast cancer is the most common subtype of breast cancer – approximately 70% of breast cancer tumours are considered HR-positive and HER2-low or negative – and the growth of HR-positive breast cancer cells is often driven by ER.
Endocrine therapies that target ER-driven disease are widely used as first-line treatment for these forms of breast cancer in the advanced setting, and often paired with CDK4/6 inhibitors. However, resistance to CDK4/6 inhibitors and current endocrine therapies develops in many patients with advanced disease and treatment options are limited, underscoring the need for additional options
Susan Galbraith, executive vice president, oncology R&D, AZ, said the results from the CAPItello-291 study “indicate that capivasertib could become a new first-in-class treatment option for patients with HR-positive breast cancer”.
Also commenting on the SERENA-2 trial results, Galbraith said: “The exciting efficacy and compelling safety results from the SERENA-2 trial underscore the potential for camizestrant to achieve this goal in patients with ER-driven breast cancer and we look forward to advancing our comprehensive phase 3 clinical programme for camizestrant.”