Yuan Yuan, MD, PhD, a medical oncologist at City of Hope, Duarte, California, said that this was yet another failed phase III trial following promising phase II data. “Entinostat was granted Fast Track designation by the U.S. Food and Drug Administration several years back based on preclinical and early clinical evidence that it reversed endocrine resistance. However, there was no benefit for entinostat in the E2112 trial,” Dr. Yuan commented.

Yuan Yuan, MD, PhD

What Next?

“As far as reasons for failure, I think we have a limited understanding of how this drug works. We have no biologic marker. These studies just scratch the surface of hormone receptor–positive/HER2-negative breast cancer. They would be more informative if we had a biomarker for patient selection,” she said.

One way to move the field forward would be to study “exceptional responders.” Dr. Yuan commented: “In every failed trial, there is always an exceptional responder, and this trial had a 4.6% response rate; among that group, there should be an exceptional responder.” 

DISCLOSURE: Dr. Yuan has served as a consultant or advisor to Eisai, Genentech, Immunomedics, Novartis, and Pfizer; has participated in a speakers bureau for Eisai and Genentech; has received research funding from Eisai, Genentech, Merck, Novartis, Pfizer, and Puma Biotechnology; and has provided expert testimony on behalf of Novartis.