Addition of Entinostat to Endocrine Therapy for Advanced Breast Cancer
Posted: Wednesday, January 27, 2021
Roisin M. Connolly, MD, of University College Cork, Ireland, and colleagues conducted the E2112 trial, which analyzed the efficacy of adding the histone deacetylase inhibitor entinostat to endocrine therapy for patients with hormone receptor–positive, HER2-negative breast cancer. The researchers discovered that although the combination therapy did not necessarily improve survival, target inhibition was confirmed in treated patients. Their work was presented at the 2020 San Antonio Breast Cancer Symposium (Abstract GS4-02).
In this multicenter, double-blind, phase III study, 608 individuals with hormone receptor–positive, HER2-negative breast cancer who experienced disease progression on a nonsteroidal aromatase inhibitor were enrolled. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 or 1, with nonmeasurable or measurable disease. Participants randomly received either exemestane plus entinostat or exemestane plus a placebo.
At study entry, 84% of participants had resistance to aromatase inhibitors in the metastatic setting, 78% had measurable disease, and 60% had visceral disease. The median number of prior chemotherapy lines was one, and 60% of participants had received prior therapy. The median lines of endocrine therapy were two. A CDK4/6 inhibitor, fulvestrant, and everolimus were previous therapies in 35%, 30%, and 3% of patients, respectively.
Adverse events of grade 3 or higher in the exemestane-plus-entinostat group included decreased neutrophils, hypophosphatemia, and anemia, which affected 20%, 14%, and 8% of patients, respectively. Other adverse events included a decreased white blood cell count (6%), fatigue (4%), diarrhea (4%), and decreased platelet counts (3%). The median progression-free survival, overall survival, and fold change in lysine acetylation in peripheral blood mononuclear cells in the combination versus placebo groups were 3.3 versus 3.1 months, 23.4 months versus 21.7 months, and 1.5 versus 1.0, respectively. The overall response rate with the combination therapy was 4.6%, and it was 4.3% with the placebo.
Disclosure: For full disclosures of study authors, visit sabcs.org.
