Evaluating the effectiveness of fulvestrant plus capivasertib in patients with aromatase inhibitor-resistant estrogen receptor-positive, HER2-negative advanced breast cancer.

This study evaluated the effectiveness of fulvestrant (Faslodex) plus capivasertib (AZD5363) in patients with aromatase inhibitor-resistant estrogen receptor-positive (ER+) and HER2-negative (HER2-) advanced breast cancer (BC). The data showed that fulvestrant plus capivasertib significantly improved the survival outcomes in these patients.

BC is classified into different subtypes depending on the presence or absence of certain receptors (proteins found on the surface of the cancer cells). ER+ and HER2- BC tests positive for the estrogen receptor (female sex hormone) and negative for the HER2 protein. This type of cancer accounts for 70% of all BCs. Patients with this subtype of BC commonly receive hormone therapy such as aromatase inhibitors (AI).

AIs such as letrozole (Femara) or anastrozole (Arimidex) reduce estrogen levels and prevent BC from coming back. However, many women can become resistant to AI treatment. These women can benefit from another hormonal treatment such as fulvestrant. Fulvestrant blocks the estrogen receptor which does not let estrogen hormone act on breast cancer cells. This stops cancer cell growth.

Capivasertib is a targeted therapy. It blocks the AKT protein which is important in regulating the cell cycle and cell growth. Blocking this protein has been shown to slow the growth of ER+ BC. The effectiveness of fulvestrant plus capivasertib in patients with AI-resistant ER+/HER2- advanced BC is still unknown.

This study involved 140 women with ER+/HER2- BC. Patients were previously treated with AIs and relapsed or progressed. Patients were randomly assigned into 2 groups. Group 1 included 69 patients who received fulvestrant plus capivasertib. Group 2 included 71 patients who received fulvestrant plus placebo. The average follow-up time was 58.5 months for group 1 and 62.3 months for group 2.

The average survival without cancer worsening was 10.3 months for group 1 versus 4.8 months for group 2. Patients in group 1 were 44% more likely to survive without cancer worsening than patients in group 2.

The average overall survival was 29.3 months for group 1 versus 23.4 months for group 2. Patients in group 1 were 34% more likely to have a better survival than patients in group 2.

In patients with PI3K/AKT/PTEN pathway-altered cancer, the average survival without cancer worsening was 12.8 months for group 1 versus 4.6 months for group 2. Patients in group 1 were 56% more likely to survive without cancer worsening than patients in group 2.

In patients with PI3K/AKT/PTEN pathway-altered cancer, the average overall survival was 38.9 months for group 1 versus 20 months for group 2. Patients in group 1 were 54% more likely to have a better survival than patients in group 2.

The most common serious side effects were high blood pressure (32% in group 1 compared to 25% in group 2), diarrhea (14% in group 1 compared to 4% in group 2), and rash (20% in group 1 and 0% in group 2). One serious case of lung infection and one death to lung infection were reported in group 1 that were considered in relation to capivasertib treatment. 

This study concluded that fulvestrant plus capivasertib significantly improved the survival outcomes in patients with AI-resistant ER+/HER2- advanced BC.

This study was sponsored by AstraZeneca, the manufacturer of capivasertib.