Hannah Linden, MD, discusses AMEERA-1: the phase 1/2 study of amcenestrant, an oral selective ER degrader (SERD), with palbociclib (palbo) in postmenopausal women with ER-positive/HER2-negative metastatic breast cancer, presented at the 2021 ASCO Annual Meeting.

Transcript

My name is Hannah Linden. I am a medical oncologist at the University of Washington and Seattle Cancer Care Alliance and the Fred Hutchinson Cancer Research Center. I am here to talk about a couple abstracts we're presenting at the upcoming ASCO meeting.

I had the honor of participating in these studies and have actually been working with these experimental agents for a bit and am excited to see them moving forward. We are excited to share the information with our colleagues.

The first abstract I want to talk about is AMEERA-1, which is a phase 1/2 study of amcenestrant, which is an oral selective estrogen receptor degrader, or SERD, in combination with palbociclib in postmenopausal women with ER-positive, HER2-negative advanced breast cancer.

The SERDs and palbociclib are changing the landscape of metastatic breast cancer. Standard of care in this setting has been an aromatase inhibitor with a CDK4/6 inhibitor, but we know that fulvestrant, the only FDA-approved SERD, which displaces the SERM tamoxifen, is actually very active early in metastatic breast cancer.

We are excited about the promise of the oral agents, which avoid the punitive injection by having oral bioavailability.

We have previously presented data showing the activity of this agent and showing that FES PET shows blockade of the receptor.

What is interesting about the current study is we combined it with a CDK4/6 inhibitor and saw to it to determine the appropriate dose moving forward. What we found is that a higher dose of this selective molecularly targeted agent reduced the dose of palbociclib.

Therefore, we backed down to the 200 milligram dose, which is a very active dose. Frankly, even lower doses are active, and we know that from our preclinical and clinical work, including the estrogen receptor imaging.

I am not worried that we have backed down on the dose. In fact, I am relieved, because I think with these molecularly targeted agents, it is important that we not overdose these patients. If you push hard enough, I think you're going to find a side effect.

I think the benefit of this agent is that it does not have much in the way of side effects. We want to keep it that way for patients, because many patients end up on these drugs for long periods of time. They get marvelous disease control, but we want them to have a very high quality of life and have a tolerable side effect profile.

Really, the only side effects we saw in the trial are really from known side effects of the class of agents of CDK4/6 inhibitors, which is really cytopenias. In this trial, at the 200-milligram dose, we saw an overall response rate of 34 percent in the first, second, and third-line setting, and a clinical benefit rate of 74 percent.

Patients remained still on the drug at the time of the presentation, with up to 72 weeks of continuous treatment. Waterfall plots and spider plots are impressive, showing clear response and long-term benefit for patients.

We are excited about this drug, and it will be moving forward in a phase-three study, comparing it with an AI and palbo.

There are several other oral SERDs in development, some of which are going to be presented at the meeting. I think they are all promising, and I am sure many will be moving forward. I think the question is which one will physicians want to give? Surely, that is going to be the one with the fewest side effects.

We did not see any cardiac signal or any other concerning signals for poor tolerability that will limit the use of this agent. We are excited about this moving forward, and I think the phase 3 trial is already accruing rapidly.