Truqap Combo Earns EU Approval for Advanced Breast Cancer

Truqap (capivasertib, AstraZeneca) in combination with Faslodex (fulvestrant) has been approved by the European Commission for the treatment of adult patients with: 

• estrogen receptor (ER)-positive,
• human epidermal growth factor receptor 2 (HER2)‑negative,
• locally advanced or metastatic breast cancer with one or more PIK3CA, AKT1, or PTEN alterations;
• and who have experienced recurrence or progression on or after an endocrine-based regimen.

Breast cancer is the most common cancer in women in the WHO European region, with an estimated 604,900 cases in 2022 and approximately 160,000 deaths. 

Approximately 70% of human breast tumors express estrogen and/or progesterone receptors, with ERs the primary transcription factor driving oncogenesis. Mutations in PIK3CA and AKT1, and alterations in PTEN, are common, affecting approximately 50% of patients with advanced HR-positive breast cancer.

Capivasertib is an AKT inhibitor that targets the cancer-driving protein molecule AKT. It locks into a cavity in the target protein to block its cancer-driving activity. It is taken orally in combination with fulvestrant, a selective estrogen receptor downregulator.

The European Union (EU)-wide approval follows the positive opinion from the European Medicines Agency’s Committee for Medicinal Products for Human Use. It is based on results from the phase 3 CAPItello-291 trial, published in The New England Journal of Medicine.

The multicenter trial enrolled 708 patients with locally advanced or metastatic hormone receptor–positive, HER2-negative breast cancer, including 289 patients with AKT pathway alterations.

Participants (18 years or older) had histologically confirmed disease that had recurred or progressed during or after treatment with an aromatase inhibitor, with or without a CDK4/6 inhibitor, and up to one line of chemotherapy for advanced disease. 

Patients were randomly assigned 1:1 to receive Truqap plus Faslodex or placebo plus Faslodex. The dual primary endpoints were progression-free survival in the overall patient population and in those with AKT pathway-altered tumors. Secondary endpoints included overall survival, objective response rate, and safety.

The trial showed that Truqap in combination with Faslodex reduced the risk for disease progression or death by 50% compared with placebo plus Faslodex in patients with tumors having PI3K, AKT1, or PTEN alterations (hazard ratio, 0.50; 95% CI, 0.38-0.65; P ≤.001; median progression-free survival, 7.3 vs 3.1 months).

The safety profile of Truqap plus Faslodex was consistent with previous trials evaluating this combination. Adverse events leading to discontinuation occurred in 13% of patients receiving Truqap, compared with 2.3% of those on the placebo.

Dave Fredrickson, executive vice president of AstraZeneca’s Oncology Business Unit, said in a press release that Truqap is the first AKT inhibitor approved in the EU for patients with ER-positive breast cancer who have tumors harboring these specific biomarkers. The approval marks a significant advancement, providing an important new treatment option for patients in need of innovative therapies.

Regulatory applications for this combination are currently under review in China and several other countries. Similar indications for Truqap in combination with Faslodex are already approved in the United States, Japan, and several other countries, based on the CAPItello-291 trial results.