Chemical compound
Elacestrant
Pronunciation
EL -ə-SES -trənt
Trade names Orserdu Other names RAD-1901; ER-306323
License data
Routes of administration
By mouth
ATC code
Legal status
Bioavailability ~10%
[1]
Protein binding >99%
[1]
Metabolism
Liver (major:
CYP3A4 , minor:
CYP2A6 ,
CYP2C9 )
[1]
Elimination half-life 30–50 hours
[1]
Excretion
Feces (82%),
urine (7.5%)
[1]
(6R )-6-{2-[Ethyl({4-[2-(ethylamino)ethyl]phenyl}methyl)amino]-4-methoxyphenyl}-5,6,7,8-tetrahydronaphthalen-2-ol
CAS Number
PubChem
CID
DrugBank
ChemSpider
UNII
KEGG
ChEMBL
PDB ligand
ECHA InfoCard
100.312.890
Formula C 30 H 38 N 2 O 2
Molar mass 458.646 g·mol−1 3D model (
JSmol )
CCNCCC1=CC=C(C=C1)CN(CC)C2=C(C=CC(=C2)OC)C3CCC4=C(C3)C=CC(=C4)O
InChI=1S/C30H38N2O2/c1-4-31-17-16-22-6-8-23(9-7-22)21-32(5-2)30-20-28(34-3)14-15-29(30)26-11-10-25-19-27(33)13-12-24(25)18-26/h6-9,12-15,19-20,26,31,33H,4-5,10-11,16-18,21H2,1-3H3/t26-/m1/s1
Key:SIFNOOUKXBRGGB-AREMUKBSSA-N
Elacestrant , sold under the brand name Orserdu , is an
anticancer medication which is used in the treatment of
breast cancer .
[1]
[4] It is taken
by mouth .
[1]
[4]
Elacestrant is an
antiestrogen , or an
antagonist of the
estrogen receptors , the
biological targets of
endogenous
estrogens such as
estradiol .
[1] The most common
side effects of elacestrant include
musculoskeletal pain ,
nausea ,
increased cholesterol ,
elevated liver enzymes ,
increased triglycerides ,
fatigue ,
decreased hemoglobin ,
vomiting ,
increased ALT ,
increased AST ,
decreased sodium ,
increased creatinine ,
decreased appetite ,
diarrhea ,
headache ,
constipation ,
abdominal pain ,
hot flashes , and
upset stomach .
[2]
Elacestrant was approved for medical use in the United States in January 2023,
[1]
[2]
[5]
[6] and in the European Union in September 2023.
[3]
[7]
Medical uses
Elacestrant is
indicated for the treatment of
postmenopausal women or adult men with
estrogen receptor (ER)-positive, human
epidermal growth factor receptor 2 (HER2)-negative,
ESR1 -
mutated
advanced or metastatic breast cancer with
disease progression following at least one line of
endocrine therapy .
[2]
[4]
Pharmacology
Pharmacodynamics
Elacestrant is an
antiestrogen , or an
antagonist of the
estrogen receptors , the
biological targets of
endogenous
estrogens like
estradiol .
[1] It is specifically an antagonist of the
estrogen receptor alpha (ERα).
[1] Elacestrant is also a
selective estrogen receptor degrader (SERD), in that it induces degradation of the ERα.
[1]
[8]
Pharmacokinetics
The
oral
bioavailability of elacestrant is approximately 10%.
[1] Its
plasma protein binding is greater than 99% and is independent of concentration.
[1] Elacestrant is
metabolized in the
liver , primarily by the
cytochrome P450
enzyme
CYP3A4 and to a lesser extent by
CYP2A6 and
CYP2C9 .
[1] The
elimination half-life of elacestrant is 30 to 50 hours.
[1] It is
excreted 82% in
feces and 7.5% in
urine .
[1]
History
Efficacy was evaluated in EMERALD (NCT03778931), a randomized, open-label, active-controlled, multicenter trial that enrolled 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer of which 228 participants had ESR1 mutations.
[2] Participants were required to have disease progression on one or two prior lines of endocrine therapy, including one line containing a CDK4/6 inhibitor.
[2] Eligible participants could have received up to one prior line of chemotherapy in the advanced or metastatic setting.
[2] Participants were randomized (1:1) to receive elacestrant 345 mg orally once daily (n=239) or investigator’s choice of endocrine therapy (n=239), which included fulvestrant (n=166) or an aromatase inhibitor (n=73).
[2] Randomization was stratified by ESR1 mutation status (detected vs. not detected), prior treatment with fulvestrant (yes vs. no), and visceral metastasis (yes vs. no).
[2] ESR1 mutational status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) using the Guardant360 CDx assay and was limited to ESR1 missense mutations in the ligand binding domain.
[2]
The FDA granted the application for elacestrant
priority review and
fast track designations.
[2]
Research
It is a
nonsteroidal combined
selective estrogen receptor modulator (SERM) and
selective estrogen receptor degrader (SERD) (described as a "SERM/SERD hybrid (SSH)") that was discovered by
Eisai and is under development by Radius Health and
Takeda for the treatment
estrogen receptor (ER)-positive advanced
breast cancer .
[9] Elacestrant has dose-dependent, tissue-selective
estrogenic and
antiestrogenic activities, with biphasic weak
partial agonist activity at the ER at low doses and
antagonist activity at higher doses.
[10] It shows agonistic activity on
bone and antagonistic activity on
breast and
uterine tissues.
[11] Unlike the SERD fulvestrant, elacestrant is able to readily cross the
blood-brain-barrier into the
central nervous system , where it can target breast cancer
metastases in the
brain ,
[10]
[11] and is
orally
bioavailable and does not require
intramuscular injection .
[10]
[11]
References
^
a
b
c
d
e
f
g
h
i
j
k
l
m
n
o
p
q
r
"Orserdu- elacestrant tablet, film coated" . DailyMed . 8 February 2023.
Archived from the original on 11 February 2023. Retrieved 11 February 2023 .
^
a
b
c
d
e
f
g
h
i
j
k
"FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer" . U.S.
Food and Drug Administration (FDA) . 27 January 2023.
Archived from the original on 2 February 2023. Retrieved 1 February 2023 . This article incorporates text from this source, which is in the
public domain .
^
a
b
"Orserdu Product information" . Union Register of medicinal products . 18 September 2023. Retrieved 1 October 2023 .
^
a
b
c
d
"Orserdu EPAR" .
European Medicines Agency (EMA) . 9 October 2023. Retrieved 9 October 2023 .
^
https://www.accessdata.fda.gov/drugsatfda_docs/appletter/2023/217639Orig1s000ltr.pdf
Archived 2023-02-02 at the
Wayback Machine This article incorporates text from this source, which is in the
public domain .
^
"Stemline Therapeutics Inc., a wholly owned subsidiary of Menarini Group, Receives Approval from U.S. FDA for Orserdu (elacestrant) as the First and Only Treatment Specifically Indicated for Patients with ESR1 Mutations in ER+, HER2- Advanced or Metastatic Breast Cancer" . Radius (Press release). 31 January 2023.
Archived from the original on 2 February 2023. Retrieved 1 February 2023 .
^
"EC approves Menarini Group's Orserdu for advanced or metastatic breast cancer" . PMLive . 21 September 2023. Retrieved 22 September 2023 .
^ Lloyd MR, Wander SA, Hamilton E, Razavi P, Bardia A (2022).
"Next-generation selective estrogen receptor degraders and other novel endocrine therapies for management of metastatic hormone receptor-positive breast cancer: current and emerging role" . Therapeutic Advances in Medical Oncology . 14 : 17588359221113694.
doi :
10.1177/17588359221113694 .
PMC
9340905 .
PMID
35923930 .
^ Clinical trial number
NCT03778931 for "Phase 3 Trial of Elacestrant vs. Standard of Care for the Treatment of Patients With ER+/HER2- Advanced Breast Cancer" at
ClinicalTrials.gov
^
a
b
c Wardell SE, Nelson ER, Chao CA, Alley HM, McDonnell DP (October 2015).
"Evaluation of the pharmacological activities of RAD1901, a selective estrogen receptor degrader" . Endocrine-Related Cancer . 22 (5): 713–724.
doi :
10.1530/ERC-15-0287 .
PMC
4545300 .
PMID
26162914 .
^
a
b
c Garner F, Shomali M, Paquin D, Lyttle CR, Hattersley G (October 2015).
"RAD1901: a novel, orally bioavailable selective estrogen receptor degrader that demonstrates antitumor activity in breast cancer xenograft models" . Anti-Cancer Drugs . 26 (9): 948–956.
doi :
10.1097/CAD.0000000000000271 .
PMC
4560273 .
PMID
26164151 .
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