FDA Approves Truqap, Faslodex for HR-Positive Breast Cancer

On November 16, 2023, the United States Food and Drug Administration approved AstraZeneca’s Truqap (capivasertib) to be administered in combination with fulvestrant for adults with hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR-positive, HER2-negative) locally advanced or metastatic breast cancer. Adding to the existing arsenal of FDA-approved breast cancer therapeutics, this combination is indicated in patients with one or more PIK3CA/AKT1/PTEN alterations.

According to the press release from AstraZeneca, HR-positive breast cancer is the most common breast cancer subtype. Among patients with HR-positive breast cancer, approximately 65% are HER2-negative or have low HER2 concentrations. Additionally, nearly 50% of patients with HR-positive breast cancer mutations in PIK3CA or AKT1 and alterations in PTEN. Considering the large proportion of patients affected by this cancer subtype and these mutations, researchers anticipate that the combinatory approach could benefit many patients.

The FDA approved the drug combination based on the results of CAPItello-291, a randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trial.

Researchers recruited over 700 patients with locally advanced or metastatic HR-positive, HER2-negative breast cancer. Nearly 300 of the participants also had tumors with one or more PIK3CA/AKT1/PTEN alterations.

Participants were randomly assigned to receive 400 mg of oral capivasertib or placebo twice daily for four days. Following every four days of treatment, patients had three days off. The cycle continued for a four-week treatment cycle. Both trial groups had an intramuscular injection of 500 mg fulvestrant on the first and fifteenth day of the first cycle. After the first treatment cycle, they received 500 mg of fulvestrant once every four weeks.

Across patients with PIK3CA/AKT1/PTEN alterations, the median progression-free survival was 7.3 months in the experimental group and only 3.1 months in the placebo-controlled group, indicating that the drug combination could effectively treat the condition.

However, patients without the PIK3CA/AKT1/PTEN alterations did not experience the same beneficial effects.

“Patients with advanced HR-positive breast cancer typically experience tumor progression or resistance with widely used first-line endocrine therapies, and there is an urgent need to extend the effectiveness of these approaches. The combination of capivasertib and fulvestrant, a first-of-its-kind combination, provides a much-needed new treatment option for up to half of patients in this setting with these specific biomarkers, offering the potential to delay disease progression and provide more time with their disease under control,” noted Komal Jhaveri, MD, Medical Oncologist, Memorial Sloan Kettering Cancer Center, in the AstraZeneca press release.