LONDON: AstraZeneca announced that its drug Truqap (capivasertib) has received approval from the US Food and Drug Administration (FDA) for the treatment of a specific type of advanced breast cancer.

Truqap is a first-in-class medicine that targets the PI3K/AKT pathway, which is involved in cancer growth and resistance to therapy.

Truqap is approved for use in combination with another drug, Faslodex (fulvestrant), for adult patients with hormone receptor (HR)-positive, HER2-negative locally advanced or metastatic breast cancer that has one or more biomarker alterations (PIK3CA, AKT1 or PTEN).

These biomarker alterations affect up to 50% of patients with this type of breast cancer and are associated with poor prognosis. Patients eligible for Truqap will have progressed on at least one endocrine-based regimen in the metastatic setting or experienced recurrence on or within 12 months of completing adjuvant therapy.

The approval was based on the results from a Phase III clinical trial, which showed that Truqap plus Faslodex reduced the risk of disease progression or death by 50% compared to Faslodex alone in patients with tumours harbouring PI3K/AKT pathway biomarker alterations.

The trial also demonstrated a significant improvement in overall survival for Truqap plus Faslodex versus Faslodex alone.

The FDA also approved a companion diagnostic test to detect the relevant biomarker alterations in patients’ tumours. The test will help identify patients who are most likely to benefit from Truqap.

Truqap is the first drug to be approved under Project Orbis, a framework for concurrent submission and review of oncology medicines among participating international partners.

Truqap is also under review by regulatory authorities in Australia, Brazil, Canada, Israel, Singapore, Switzerland and the UK. In addition, regulatory applications for Truqap in combination with Faslodex are currently under review in China, the European Union, Japan and several other countries.

Truqap was developed by AstraZeneca in collaboration with Astex Therapeutics, a subsidiary of Otsuka Pharmaceutical Co., Ltd. Astex Therapeutics is eligible to receive a milestone payment from AstraZeneca following the US approval of Truqap.

Breast cancer is the most common cancer and one of the leading causes of cancer-related death worldwide. More than two million patients were diagnosed with breast cancer in 2020, with nearly 685,000 deaths globally.

In the US, more than 290,000 patients are expected to be diagnosed in 2023, with more than 43,000 deaths.

HR-positive breast cancer (expressing estrogen or progesterone receptors, or both), is the most common subtype of breast cancer with more than 65% of tumours considered HR-positive and HER2-low or HER2-negative.

Collectively, mutations in PIK3CA, AKT1 and alterations in PTEN occur frequently, affecting up to 50% of patients with advanced HR-positive breast cancer.

The growth of HR-positive breast cancer cells is often driven by estrogen receptors (ER), andendocrine therapies that target ER-driven disease are widely used as first-line treatment 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.

Once this occurs, treatment options are limited – with chemotherapy being the current standard of care – and survival rates are low with 30% of patients anticipated to live beyond five years after diagnosis.

The optimisation of endocrine therapy and overcoming resistance to enable patients to continue benefiting from these treatments, as well as identifying new therapies for those who are less likely to benefit, are active areas of focus for breast cancer research.

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