AstraZeneca’s (AZ) AKT inhibitor Truqap (capivasertib) in combination with its endocrine therapy Faslodex (fulvestrant) has been recommended by the European Medicines Agency’s human medicines committee to treat a subset of advanced breast cancer patients.
The Committee for Medicinal Products for Human Use (CHMP) has recommended that the combination be used in adults with oestrogen receptor (ER)-positive, HER2 negative locally advanced or metastatic breast cancer with at least one of three biomarker alterations: PIK3CA, AKT1 or PTEN.
Eligible patients will also have experienced disease recurrence or progression on or after an endocrine-based regimen.
Breast cancer remains the leading cause of cancer death in Europe, where more than 550,000 new cases of the disease were diagnosed in 2022.
Hormone receptor (HR)-positive breast cancer is the most common subtype, with about 70% of tumours considered HR-positive and HER2-low or HER2-negative, and mutations in PIK3CA, AKT1 and alterations in PTEN affect approximately 50% of patients with advanced HR-positive breast cancer.
HR-positive breast cancer progression is often driven by ERs, and endocrine therapies that target ER-driven disease are widely used as a first-line treatment in the advanced setting and often paired with CDK4/6 inhibitors. However, resistance to these therapies develops in many patients with advanced disease.
The CHMP’s decision on AZ’s combination was supported by positive results from the late-stage CAPItello-291 trial, in which Truqap plus Faslodex reduced the risk of disease progression or death by 50% compared with Faslodex alone in patients with tumours harbouring PI3K, AKT pathway or PTEN alterations.
Susan Galbraith, executive vice president, oncology research and development, AZ said: “[The] news reinforces the practice-changing potential of Truqap in combination with Faslodex to extend the effectiveness of endocrine-based treatment approaches for patients who experience tumour progression on, or resistance to, widely used endocrine-based therapies.
“This recommendation recognises the high unmet need in this biomarker-specific patient population, and if approved, patients in Europe with this specific type of disease may be able to benefit from this first-in-class treatment option.”
Similar indications for Truqap, which was discovered by AZ subsequent to a collaboration with Astex Therapeutics, in combination with Faslodex are already approved in the US and several other countries based on results from CAPItello-291.