Hannah Linden, MD, highlights the efficacy of enobosarm, a selective AR targeting agent, correlating with the degree of AR positivity in advanced AR/ER-positive breast cancer, an international phase 2 clinical study presented at the 2021 ASCO Annual Meeting.

Transcript

The other abstract I wanted to talk about is one we have presented it is data we have presented previously as well, but this is a new analysis of a drug that has been out there for a while, and I hope will find a home soon. It is now with a different company.

This study is called the Efficacy of Enobosarm, a Selective Androgen Receptor Targeting Agent, and correlates with the degree of AR positivity in advanced androgen receptor-positive, estrogen receptor-positive in an international phase-two clinical study.

This multicenter effort was to look at a novel approach in breast cancer. This is like the tamoxifen of androgens. It is a selective androgen receptor modulator, a SARM. This is exciting, because most ER-positive tumors are androgen receptor-positive.

Having a different endocrine pathway to manipulate for clinical benefit offers a patient a chance to avoid the known and annoying side effects of endocrine manipulation of the ER pathway. It gives patients a break from the menopausal symptoms, and actually gives them some favorable side effects that made this trial an extremely appealing one to participate in.

The vast majority of ER-positive patients at presentation will be androgen receptor-positive. We did measure their androgen receptor positivity, and that is the important new piece of information in this trial. We looked at a couple different doses of enobosarm, the SARM, and found that it was quite active and quite well-tolerated.

Patients feel well on this, do not have virilization, other masculinization-type side effects that we see with testosterone, such as acne, hirsutism, or anger, which is a side effect when you give testosterone to patients, but they do feel actually like they have a little more energy, and like they are able to build lean body mass more effectively on this agent. Notably, they do not have hot flashes, and they do not have joint aches.

Patients participated in the trial and experienced a clinical benefit. When we analyzed the degree of androgen receptor positivity and the clinical benefit, we found that the patients with tumors with greater than 40-percent androgen receptor expression were the ones who had the most clinical benefit.

In that group, which is the majority of the patients, 80 percent had clinical benefit, and 48 percent had an objective response rate, with some patients remaining on the drug with ongoing clinical benefit. Therefore, based on these promising findings, we are embarking on a phase-three study to test this agent against standard endocrine therapy.

I think this is really good news for breast cancer patients. Even though in general, our patients do well and get clinical benefit, many of them really find the anti-estrogen effects to be quite crippling and frustrating to have to live with.

This is an alternative agent that makes patients feel better, and gives them a little bit more energy and a little bit more physical strength, which is extremely appealing, as we know that exercise and overall fitness is good for breast cancer, and it is good for their overall health and their issues.

I think we have seen in prostate cancer that endocrine treatments can really impair quality of life and have cardiac impacts. We would like to have alternative therapies to give patients that do not have these undesirable side effects.

We are very excited about this agent, and I hope we are successful in moving forward with these trials, so that more women can have access to drugs that are frankly much more appealing long-term, and we do not see a long-term downside to this.

Obviously, everybody does not respond to endocrine therapy, and this is not going to benefit everyone, but it is going to benefit a significant subset of patients and it is a very appealing agent.

I think the question I can hear being asked in the background is, "What about triple-negative AR-positive?" That has not been looked at as yet. Thank you for your attention.