SAN FRANCISCO Clinical benefit from use of a novel histone deacetylase inhibitor drug may be determined by examining blood cells days after a patient receives treatment. The drug, entinostat, is the first histone deacetylase inhibitor successfully tested in a randomized, placebo-controlled study in metastatic breast cancer and is the first to show that clinical outcome can be predicted shortly after administration.
The findings, reported at the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics, held Nov. 12-16, 2011, represent an advance in the goal to offer patients only those therapies that will help treat cancer effectively, the researchers said.
"The ability to have a marker of benefit within the first several weeks of using this drug represents an exciting advance in personalized medicine," said lead researcher Peter Ordentlich, Ph.D., executive director of translational science and a founder of Syndax Pharmaceuticals Inc. in Waltham, Mass. Syndax Pharmaceuticals developed entinostat, an oral small-molecule drug that inhibits enzymes that alter the packaging of DNA inside the nucleus, which controls gene expression.
"The goal of entinostat in breast cancer is to extend the benefit of hormone therapy and delay the time that patients will need to use chemotherapy," said Ordentlich. More than 160,000 women are diagnosed each year with estrogen receptor (ER)-positive invasive breast cancer, and many are treated with agents that block the hormone. But most women become resistant to these therapies, and entinostat, combined with antihormone agents, is meant to extend their benefit, he said.
To test that strategy in ER-positive metastatic breast cancer, Syndax Pharmaceuticals conducted ENCORE-301, a randomized, placebo-controlled, phase 2 study (n=130) testing the use of exemestane, an aromatase inhibitor, with either entinostat or placebo.
Results of the clinical trial, released in
|Contact: Jeremy Moore|
American Association for Cancer Research