Managing ESR1-Mutated ER-Positive Breast Cancer with Imlunestrant & Abemaciclib
|
Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on April 30th, 2025
|
Estrogen receptor (ER)-positive breast cancer can be managed with ER antagonists like fulvestrant. However, fulvestrant’s requirement for intramuscular injection complicates treatment, necessitating clinic visits and limiting its convenience. Furthermore, its efficacy is reduced in patients with ESR1 mutations in the estrogen receptor. Imlunestrant is a newer, orally available ER antagonist. To evaluate its effectiveness, Eli Lilly sponsored a study combining imlunestrant with abemaciclib in managing ER-positive, HER2-negative breast cancer.
The phase 3 clinical trial enrolled 874 patients with ER-positive, HER2-negative breast cancer, with a median age of 61 years; nearly 90% were postmenopausal. ESR1 mutations were present in 30–40% of participants, and about 75% had progesterone receptor–positive tumors. Most had prior exposure to CDK4/6 inhibitors, predominantly palbociclib, while fewer than 10% had previously received abemaciclib. Participants were randomized into three treatment groups: standard endocrine therapy (oral exemestane or intramuscular fulvestrant, per physician discretion), imlunestrant monotherapy (400 mg orally daily), or imlunestrant plus abemaciclib (150 mg orally twice daily). Abemaciclib is a CDK4/6 inhibitor that suppresses tumor cell proliferation and has demonstrated benefit in breast cancer treatment. Among patients with ESR1 mutations, imlunestrant alone significantly extended progression-free survival (PFS) to 5.5 months—2.6 months longer than standard endocrine therapy. No such benefit was seen in patients without ESR1 mutations. Notably, the combination of imlunestrant and abemaciclib further extended PFS to 9.4 months. However, this regimen was associated with a higher incidence of side effects, including fatigue, diarrhea, nausea, and anemia.
The phase 3 clinical trial enrolled 874 patients with ER-positive, HER2-negative breast cancer, with a median age of 61 years; nearly 90% were postmenopausal. ESR1 mutations were present in 30–40% of participants, and about 75% had progesterone receptor–positive tumors. Most had prior exposure to CDK4/6 inhibitors, predominantly palbociclib, while fewer than 10% had previously received abemaciclib. Participants were randomized into three treatment groups: standard endocrine therapy (oral exemestane or intramuscular fulvestrant, per physician discretion), imlunestrant monotherapy (400 mg orally daily), or imlunestrant plus abemaciclib (150 mg orally twice daily). Abemaciclib is a CDK4/6 inhibitor that suppresses tumor cell proliferation and has demonstrated benefit in breast cancer treatment. Among patients with ESR1 mutations, imlunestrant alone significantly extended progression-free survival (PFS) to 5.5 months—2.6 months longer than standard endocrine therapy. No such benefit was seen in patients without ESR1 mutations. Notably, the combination of imlunestrant and abemaciclib further extended PFS to 9.4 months. However, this regimen was associated with a higher incidence of side effects, including fatigue, diarrhea, nausea, and anemia.