approvFrom: oncologynurseadvisor.com
The Food and Drug Administration (FDA) has approved Inluriyo (imlunestrant) for the treatment of adults with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-), ESR1-mutated advanced or metastatic breast cancer whose disease progressed after at least 1 line of endocrine therapy.
The approval was based on data from the randomized, open-label, active-controlled, phase 3 EMBER-3 trial (ClinicalTrials.gov Identifier: NCT04975308), which evaluated imlunestrant, an oral estrogen receptor antagonist, in adults with ER+, HER2- locally advanced or metastatic breast cancer, who were previously treated with an aromatase inhibitor either alone or in combination with a CDK4/6 inhibitor.
Study participants were randomly assigned 1:1:1 to receive imlunestrant 400mg once daily (n=138); an investigator’s choice of endocrine therapy (n=118; fulvestrant 500mg intramuscularly on days 1, 15, 29 then once monthly thereafter or exemestane 25mg once daily); or an additional investigational combination regimen, until disease progression or unacceptable toxicity. The primary endpoint was investigator-assessed progression free survival according to RECIST v1.1.
ESR1m status was determined by blood circulating tumor deoxyribonucleic acid (ctDNA) analysis using the Guardant360 CDx assay, a companion diagnostic that has also been FDA-approved to identify patients with ESR1-mutated breast cancer.
In the ESR1m population, imlunestrant significantly reduced the risk of disease progression or death by 38% vs investigator’s choice of endocrine therapy (hazard ratio, 0.62 [95% CI, 0.46-0.82]; P =.0008); median PFS was 5.5 months (95% CI, 3.9-7.4) and 3.8 months (95% CI, 3.7-5.5), respectively.
Results also showed that the objective response rate was 14.3% in the imlunestrant arm (complete response: 0.9%; partial response: 13.4%) compared with 7.7% in the endocrine therapy arm (complete response: 0%; partial response: 7.7%). At the time of analysis, overall survival data were immature, with 31% of deaths reported in the ESR1-mutated population.
The most common adverse reactions reported with treatment were decreased hemoglobin, musculoskeletal pain, decreased hemoglobin, decreased calcium, decreased neutrophils, increased aspartate aminotransferase, fatigue, diarrhea, increased alanine aminotransferase, increased triglycerides, nausea, decreased platelets, constipation, increased cholesterol, and abdominal pain.
Inluriyo is supplied as 200mg tablets. The recommended dosage is 400mg once daily taken on an empty stomach at least 2 hours before food or 1 hour after food. Prior to initiation, patients should be selected for treatment based on the presence of ESR1 mutations.
Pre- and perimenopausal women and men should receive gonadrotropin-releasing hormone agonists based on current clinical practice standards. Dosage modifications may be required to manage adverse reactions, as well as for patients with moderate or severe hepatic impairment and those taking concomitant strong CYP3A inhibitors and inducers.
According to Lilly, Inluriyo is expected to be available in the coming weeks.
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