AMEERA-1: Phase 1-2 Study of Amcenestrant, An Oral Selective Estrogen Receptor Degrader, With Palbociclib in Postmenopausal Women With ER+ HER2- Metastatic Breast Cancer - Episode 5
Dr Chandarlapaty discusses the AMEERA-1 trial and its impact on the ER+/HER2- metastatic breast cancer landscape.
Sarat Chandarlapaty, MD: The AMEERA-1 study comprised multiple arms looking at first the single agent and then combinations. Part A of the AMEERA-1 study was the first-in-human dose escalation looking at doses anywhere from 20 to 600 mg. The B component was an expansion of the study using 400 mg as a single agent. Part C was to look at the standard combination of antiestrogen with CDK4 inhibitor, in this case palbociclib, and part C, doses of 200 and 400 mg were looked at in combination with standard dosing of palbociclib. Then in part D, there was an expansion of that combination using the 200-mg dose of amcenestrant. There are subsequent arms that are enrolling, looking at other combinations such as with alpelisib, abemaciclib, and everolimus.
The main findings of the studies, part A and B, were designed to look at the safety of the single agent, showing it to be a very pure antiestrogen with adverse effects such as hot flashes in about 30%, 40% of patients and no grade 3 adverse events. In that study in patients who at least got to be what we consider to be an efficacious dose at 150 mg and above, clinical benefit was seen in about 35% of patients. That number goes up further if you look at the patients who hadn’t received as much prior therapy like targeted therapy. A very effective hormone therapy in this patient population.
Then part C and D looked at the combination with palbociclib. When you looked at the safety signal for that combination, what you saw was essentially the adverse-effect profile of the 2 single agents added together. You’ve got the adverse effects of Ibrance [palbociclib], and you’ve got the adverse effects of amcenestrant. But there were no synergistic or unique toxicities from the combination.
In that study in the patients who were evaluable, 74% of patients had clinical benefit. That strongly supported the opening of the AMEERA-5 clinical trial, which was looking at a randomized study in the first-line setting, in which all patients get palbociclib or patients are randomized to get standard-of-care letrozole as their hormone therapy or amcenestrant as their hormone therapy.
Right now, amcenestrant is not a clinically approved agent. What we’ve seen in terms of the adverse-effect profile, in terms of the potency of the agent and inhibiting the estrogen receptor, strongly support the growing program of AMEERA trials that are widely available in larger phase 3 trials looking at amcenestrant in the advanced setting in combination with a CDK4 inhibitor. Looking at amcenestrant in the early-stage setting, a trial that’s soon to open looking in the adjuvant setting. The data really point to us needing to, as an oncology community, evaluate this agent in large phase 3 studies.
Transcript edited for clarity.