Adding dalpiciclib to fulvestrant in patients with hormone receptor-positive and HER2-negative advanced breast cancer

This study investigated the effectiveness and safety of dalpiciclib (SHR6390) plus fulvestrant (Faslodex) in patients with hormone receptor-positive (HR+) and HER2-negative (HER2-) advanced breast cancer (BC). The data showed that adding dalpiciclib to fulvestrant was safe and significantly improved the survival without cancer worsening 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). HR+ and HER2- BC tests positive for the estrogen and/or progesterone receptor (female sex hormones) 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 fulvestrant which acts by decreasing the female hormones.

Dalpiciclib is a targeted therapy. It blocks proteins CDK4 and CDK6 that are important in regulating the cell cycle and cell growth. Blocking these proteins has been shown to slow the growth of HR+ BC. Whether adding dalpiciclib to fulvestrant therapy in patients with HR+ and HER2-negative advanced BC adds benefits to the outcomes of these patients is still under investigation.

This study involved 361 women with HR+ and HER2- advanced BC that relapsed or progressed on previous hormonal therapy. Patients were randomly assigned into 2 groups. Group 1 included 241 patients who received dalpiciclib plus fulvestrant. Group 2 included 120 patients who received a placebo plus fulvestrant. The average follow-up time was 10.7 months.

The average survival without cancer worsening was significantly longer for group 1 (15.7 months) compared to group 2 (7.2 months). Patients in group 1 were 58% more likely to survive without cancer worsening compared to patients in group 2.

After 6 months, 76.4% of the patients in group 1 were alive without cancer worsening compared to 53.3% of the patients in group 2. After 12 months, 51.8% of the patients in group 1 were alive without cancer worsening compared to 29.1% of the patients in group 2.

The overall response rate (partial or complete response to the therapy) was 27% for group 1 compared to 20% for group 2. Overall, 61% of the patients in group 1 had a clinical benefit (response to treatment or stable disease) compared to 45.8% of the patients in group 2.

Overall, 5.8% of the patients in group 1 experienced serious side effects compared to 6.7% of the patients in group 2. The most common side effects with dalpiciclib plus fulvestrant treatment were low counts of neutrophils (84.2%; white blood cells that fight off infections) and low counts of leukocytes (62.1%; white blood cells).

This study concluded that adding dalpiciclib to fulvestrant was safe and significantly improved the survival without cancer worsening in patients with HR+ and HER2- advanced BC.

The study was funded by Jiangsu Hengrui Medicine Co, the manufacturers of dalpiciclib. This study only included Chinese patients. More studies in other populations are needed to fully evaluate the benefits of adding dalpiciclib to fulvestrant.