Rebecca Dent, MD
FORMAL DISCUSSANT of the ACE trial, Rebecca Dent, MD, of the National Cancer Center in Singapore, commented that the phase II ENCORE 301 study provided proof of concept that a histone deacetylase (HDAC) inhibitor can reprogram epigenetic changes.1
In that randomized, double-blind, placebo-controlled trial, the combination of the HDAC inhibitor entinostat plus exemestane prolonged progression-free survival and reduced the risk of disease progression by 27% compared with exemestane alone. These findings led to plans for a phase III trial.
“ACE is now the second trial demonstrating a clinical benefit with the addition of HDAC inhibitors to endocrine therapy in estrogen receptor–positive advanced breast cancer. HDAC inhibitors warrant further investigation in earlier settings of advanced hormone receptor–positive breast cancer in yet-to-be-predefined subgroups. We await results of the phase III study of entinostat, as well as survival results from these studies,” Dr. Dent told the audience. “These therapies have selective actions that we don’t fully understand, and we don’t know how prior therapies affect response. We need biomarker-driven strategies.”
Suzette Delaloge, MD, MSc
ESMO EXPERT Suzette Delaloge, MD, MSc, of Institut Gustave Roussy, Paris, commented in a news release: “This is the first randomized phase III trial to reach a positive result with an HDAC inhibitor in advanced breast cancer. It suggests that there may be some hope for this type of drug in these patients; until now the only positive results have been in earlier-stage breast cancer.”
She added, “Studies are needed in Western populations comparing an HDAC inhibitor to the standard of care, which is the combination of endocrine therapy plus a [mammalian target of rapamycin] inhibitor (everolimus) or the combination of an endocrine therapy plus a [cyclin-dependent kinase]4/6 inhibitor.” ■
DISCLOSURE: Dr. Dent has received honoraria from AstraZeneca, Roche/Genentech, Pfizer, and Lilly; has been a consultant/advisor for Roche, Pfizer, Merck, Eisai, and AstraZeneca; and has received reimbursement for travel/accommodations/ expenses from Roche, Pfizer, and Amgen. Dr. Delaloge has received consulting fees from AstraZeneca, Lilly, Pfizer, and Roche; has done independent contracting for Amgen, AstraZeneca, Lilly, Novartis, Pfizer, Puma Biotechnology, Roche, and Sanofi; and has completed speaking and teaching engagements for AstraZeneca, Pfizer, and Roche.
1. Yardley DA, Ismail-Khan R, Klein P, et al: Results of ENCORE 301, a randomized, double-blind, placebo-controlled trial of exemestane with or without entinostat in postmenopausal women with locally recurrent or metastatic estrogen receptor-positive breast cancer progressing on a nonsteroidal aromatase inhibitor. 2011 Breast Cancer Symposium. Abstract 268. Presented September 9, 2011.
EPIGENETIC CHANGES are associated with the development of cancer, and epigenetic therapy is an attractive strategy for targeting the tumor microenvironment. One approach targeted to epigenetic changes is using histone deacetylase (HDAC) inhibition, which has antitumorigenic effects including growth ...