Phase II clinical trial testing the safety and efficacy of adding entinostat to exemestane therapy in hormone-resistant breast cancer patients

This phase II clinical trial tested whether a new drug, entinostat, can work in concert with exemestane (a hormone therapy drug), to fight breast cancer that no longer responds to hormone therapy alone.

Some breast cancers need estrogen (a female sex hormone) to grow. These breast cancer cells respond to estrogen via their receptor (a protein on the surface of the cells). These types of breast cancer are called estrogen receptor-positive (ER+). This means that patients with this condition can be treated with hormone therapy, which blocks the estrogen supply to the cancer, stopping the cancers growth. However, some ER+ breast cancers stop responding to hormone therapy, a process called hormone therapy resistance. Exemestane (Aromasin) is a type of hormone therapy which decreases the amount of estrogen the body produces, therefore slowing or stopping the growth of ER+ breast cancer. Entinostat is a drug that appears to act on the estrogen receptors on breast cancer cells, thus helping reduce hormone therapy resistance and also stopping the growth of ER+ breast cancers. This phase II clinical trial tested if the addition of entinostat to exemestane therapy increases sensitivity to hormone therapy in patients with breast cancer patients.

130 postmenopausal women with ER+, hormone resistant breast cancer participated in this phase II clinical trial. They were randomly assigned to reiceive either exemestane + entinostat (group EE – 64 patients) or exemestane + placebo, a substance with no medical effect used as a control in testing new drugs (group EP – 66 patients). This study determined that the EE group had 2 months more time without disease progression than the EP group (4.2 months vs. 2.2 months). Median overall survival (defined as the percentage of patients surviving after a certain time from treatment) was also longer for patients in the EE group (28.1 months) compared to patients in the EP group (19.8 months). However, patients in the EE group reported more side effects from treatment compared to patients in the EP group. The most common side effects were tiredness and increased risk of infections. 

In summary, the addition of entinostat to exemestane therapy resulted in improved survival rates, with manageable side effects in patients with ER+, hormone resistant breast cancer.

Entinostat is a promising new drug now moving on to a phase III clinical trial for patients with postmenopausal ER+ breast cancer, resistant to hormone therapy.

This study was funded by Syndax Pharmaceuticals, the manufacturer of entinostat.