AstraZeneca’s Truqap (capivasertib) in combination with Faslodex (fulvestrant) has been recommended for approval in the European Union (EU) for the treatment of adult patients with estrogen receptor (ER)-positive, HER2‑negative locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1, or PTEN-alterations following recurrence or progression on or after an endocrine-based regimen.
The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) based its positive opinion on the results from the CAPItello-291 Phase III trial published in The New England Journal of Medicine.
In the trial, Truqap in combination with Faslodex reduced the risk of disease progression or death by 50% versus Faslodex alone in patients with tumors harboring PI3K, AKT or PTEN alterations (based on hazard ratio of 0.50, 95% confidence interval 0.38-0.65; p=<0.001; median progression-free survival (PFS) 7.3 versus 3.1 months).
In Europe, breast cancer remains the leading cause of cancer death, with more than 140,000 deaths in 2022 and more than 550,000 new patients diagnosed in the same year. HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with 70% of tumors considered HR-positive and HER2-low or HER2-negative. More than 97% of HR-positive breast cancer tumors are ER-positive. Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting approximately 50% of patients with advanced HR-positive breast cancer. HR-positive breast cancer progression is often driven by estrogen receptors, and endocrine therapies that target ER-driven disease are widely used as 1st-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, and alternative approaches are needed to extend the effectiveness of endocrine-based therapies.
Mafalda Oliveira, MD, PhD, Senior Consultant at the Department of Medical Oncology, Vall d’Hebron University Hospital, and Senior Clinical Investigator of the Vall d’Hebron Institute of Oncology’s (VHIO) Breast Cancer Group in Barcelona, Spain, said: “There is an urgent need to extend the effectiveness of widely used endocrine therapies in patients with advanced ER-positive breast cancer to delay disease progression or resistance. With this combination demonstrating a fifty per cent reduction in disease progression or death in patients with tumors harboring PIK3CA, AKT1, or PTEN-alterations in the CAPItello-291 trial, this positive recommendation marks an important step in providing a much-needed new treatment option for approximately half of patients in this setting with these specific tumor biomarkers.”
Susan Galbraith, Executive Vice President, Oncology R&D, AstraZeneca, said: “Today’s 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 tumor progression on, or resistance to widely used endocrine-based therapies. This recommendation recognizes 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.”
In the CAPItello-291 trial, the safety profile of Truqap plus Faslodex was similar to that observed in previous trials evaluating this combination.
Regulatory applications are currently under review in China and several other countries, and similar indications for Truqap in combination with Faslodex are already approved in Japan, the US and several other countries based on results from the CAPItello-291 trial.
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