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Medicine Matters oncology

So the E2112 study is a large phase 3 trial in patients with advanced hormone-receptor positive breast cancer who have previously been treated with a nonsteroidal aromatase inhibitor and investigates the combination of exemestane, a steroidal aromatase inhibitor, with the HDAC inhibitor entinostat versus placebo. And the summary of this final trial results presented today is that the combination of the endocrine therapy with the HDAC inhibitor did not improve survival when compared to endocrine therapy alone.

So I think we've also been struggling with this question. We were very, very hopeful that the phase 3 would confirm the phase 2 data. I think it has made us realize and confirm the importance of phase 3 confirmation of phase 2 data. We, in designing the phase 3, aimed to mirror as closely as possible the eligibility criteria for the phase 2. There were some slight differences in that patients in the phase 3, approximately a third of them, had received prior CDK inhibitor, as an example. And similarly, a portion of patients had received prior fulvestrant which were not part of the phase 2. And so there may have been slight differences in the populations, but overall I believe that the phase 3 was necessary to confirm the phase 2 and did not do so.

So I think certainly we have shown in this setting, in advanced breast cancer, in this population previously treated with endocrine therapy, that there does not appear to be a benefit of this agent. However, there may be other populations in which this agent can be explored. And there has been an interest in the potential immune modulatory impact of this and other HDAC inhibitors, which is being explored in other studies. And so there may be still a role for HDAC inhibitors in breast cancer, but it would require a careful, again, preclinical and clinical data to support large phase 3 studies such as this.