Truqap and Faslodex approved in EU for advanced ER-positive breast cancer

On June 20, 2024, AstraZeneca announced the European Union (EU) approval of its novel drug, Truquap (capivasertib), in combination with Faslodex (fulvestrant). This approval marks a significant milestone as Truquap becomes the first and only AKT inhibitor sanctioned in the EU for treating adult patients suffering from estrogen receptor (ER)-positive, HER2-negative, locally advanced or metastatic breast cancer. To qualify, patients must have specific biomarker alterations such as PIK3CA, AKT1, or PTEN, and have experienced recurrence or progression following an endocrine-based regimen.

The European Commission's decision was heavily influenced by the results of the CAPItello-291 Phase III trial, which were published in The New England Journal of Medicine. The study demonstrated that the combination of Truquap and Faslodex significantly reduced the risk of disease progression or death by 50%, compared to Faslodex alone, in a population with tumors harboring PI3K, AKT, or PTEN alterations. The median progression-free survival was notably higher at 7.3 months for the combination therapy, versus 3.1 months for Faslodex alone.

Breast cancer remains a leading cause of cancer death in Europe, with more than 140,000 deaths and over 550,000 new diagnoses in 2022 alone. Hormone receptor (HR)-positive breast cancer, which constitutes around 70% of all breast cancer cases, is the most prevalent subtype. Approximately 50% of patients with advanced HR-positive breast cancer exhibit PIK3CA, AKT1, or PTEN mutations.

Dr. Mafalda Oliveira from Vall d’Hebron University Hospital in Barcelona emphasized the urgent need for new treatments for patients who often develop resistance to standard endocrine therapies. She highlighted the significance of identifying eligible patients who could benefit from this new combination therapy. Dave Fredrickson, Executive Vice President of AstraZeneca’s Oncology Business Unit, hailed the approval as a crucial advancement in providing innovative treatment options for breast cancer patients in Europe.

The CAPItello-291 trial was a large-scale, double-blind study that enrolled 708 adult patients with histologically confirmed HR-positive, HER2-low or negative breast cancer, whose disease had progressed during or after aromatase inhibitor therapy. The trial had dual primary endpoints focusing on progression-free survival in both the overall patient population and a subgroup with specific PI3K/AKT pathway alterations. Notably, around 40% of the tumors in the trial had these genetic alterations, and about 70% of patients had previously received a CDK4/6 inhibitor.

Truquap is a potent, first-in-class, adenosine triphosphate (ATP)-competitive inhibitor targeting all three AKT isoforms (AKT1/2/3). It is administered twice daily following an intermittent dosing schedule optimized for tolerability and efficacy. Beyond the EU, Truquap has also been approved in the US, Japan, and several other countries based on the CAPItello-291 trial results. The drug is currently being evaluated in additional Phase III trials for both breast and prostate cancer.

Faslodex, an endocrine therapy, is used to treat ER-positive, locally advanced or metastatic breast cancer, either as monotherapy or in combination with other drugs. In the US, EU, and Japan, it is also approved in combination with CDK4/6 inhibitors for advanced or metastatic breast cancer cases.

AstraZeneca continues to push the boundaries of breast cancer treatment with its comprehensive portfolio, which includes Truquap and other promising compounds under development. The company aims to redefine cancer care and ultimately eliminate breast cancer as a cause of death, driven by a deep understanding of breast cancer biology and persistent innovation.