J Clin Oncol: The efficacy and safety of the new selective ER degradation agent Elacestrant for the treatment of ER-HER2-advanced breast cancer

The Phase I RAD1901-005 study evaluated the efficacy and safety of elacestrant, an experimental oral selective estrogen-inhibitor (SERD) for estrogen-positive, human-skin growth factor-like 2-negative metastasis breast cancer patients, including those with mutations in the estrogen-infested gene α (ESR1).
this paper reports on the main objectives of the study, namely, the maximum to-to-do dose and/or the recommended phase II dose (RP2D).
the study was designed for 3 plus 3 (Elacestrant capsules), followed by an extended study with RP2D (400 mg capsules, then 400 mg tablets) to assess safety and anti-tumor activity.
elacestrant capsule once a day until the condition progresses or becomes insulable.
ESR1 gene mutation frequency recruited a total of 57 post-menoptostrual women, of whom 50 received RP2D (400 mg/day): a median age of 63 years, the median previous anti-cancer course was 3 times, including cell cycle-dependent kinase 4,6 inhibitors (CDK4/6i, 52%), SERD (52%) and ESR1 mutation (circulating DNA tumors, 50%).
the most common adverse reactions in RP2D (400 mg tablets, n-24) were malignant (33.3%), elevated triglycerides (25%) and decreased blood phosphorus (25%).
most common adverse reactions are level 1-2.
The objective remission rate of changes in the frequency of ESR1 gene mutations in treatment and correlation with treatment prognosis was 19.4% (n-31, assessable patients receiving RP2D);
rate (24 weeks) was 42.6% for the total population, and 56.5% and 30.4% for patients with ESR1 mutations and CDK4/6i treatment, respectively.
the clinical benefits of Elacestrant were associated with a decrease in allebrae scores for ESR1 mutations.
addition, oral 400mg Elacestrant daily has acceptable safety, and in patients with metastase-positive metastases, single-drug activity has been shown to be partially relieved.
note that patients with ESR1 mutations, as well as those who have previously been treated with CDK4/6i and SERD, can also receive partial remission from Elacestrant therapy.
Phase III trials comparing Elacestrant with standard endocrine therapy are under way.