The US Meals and Drug Administration accepted elacestrant (Orserdu, Stemline Therapeutics, Inc) for postmenopausal girls or males with ER-positive, HER2-negative, ESR1-mutated superior or metastatic breast most cancers that progressed on at the least one line of endocrine remedy.
The company additionally accepted the Guardant360 CDx assay as a companion diagnostic to determine breast most cancers sufferers who meet the therapy necessities, in line with the company’s press release asserting the approval.
The novel oral selective estrogen receptor degrader was accepted based mostly on the part 3 EMERALD trial, which included 478 postmenopausal men and women with ER-positive, HER2-negative superior or metastatic breast most cancers, about half of whom had ESR1 mutations. Sufferers had progressed on one or two prior traces of endocrine remedy, together with one containing a CDK4/6 inhibitor. Individuals may even have had one prior line of chemotherapy within the superior or metastatic setting.
Individuals had been randomized 1:1 to both elacestrant 345 mg orally as soon as every day or investigator’s selection of endocrine remedy, which included fulvestrant or an aromatase inhibitor.
Within the 228 sufferers (48%) with ESR1 mutations, median progression-free survival (PFS) was 3.8 months with elacestrant versus 1.9 months within the fulvestrant or aromatase inhibitor arm (hazard ratio, 0.55; P = .0005). Investigators noticed no statistically important PFS distinction between the therapy arms in sufferers who did not have the mutation.
In a Medscape Medical Information story printed in June, specialists raised issues in regards to the adequacy of the “commonplace of care” management arm in EMERALD, notably that single brokers had been used at a time when mixture remedy is changing into extra widespread.
“The expression ‘commonplace of care’ is utilized generously, because the management arm is restricted” to single brokers and no combos, which “could have led to a substandard” comparability group, Timothée Olivier, MD, Geneva College Hospital, Switzerland, and Vinay Prasad, MD, MPH, College of California San Francisco, stated in an editorial quoted within the piece.
EMERALD investigators acknowledged that there have been points with the management group, noting that within the “United States and Europe, mixture remedy with fulvestrant” — as a substitute of single brokers — “is more and more getting used because the second-line [standard of care] therapy.”
Nevertheless, the objective of the research “was to check a novel endocrine remedy vs at the moment obtainable endocrine therapies,” not mixture regimens, the investigators stated.
Additionally, “the good thing about elacestrant over fulvestrant and AIs in our monotherapy trial…means that incorporating elacestrant as the popular endocrine remedy spine in future earlier-line mixture research is a promising technique.”
Lipid Monitoring Crucial
The commonest antagonistic occasions with elacestrant, occurring in 10% or extra of sufferers, are musculoskeletal ache, nausea, elevated ldl cholesterol, elevated AST, elevated triglycerides, fatigue, decreased hemoglobin, vomiting, elevated ALT, decreased sodium, elevated creatinine, decreased urge for food, diarrhea, headache, constipation, stomach ache, sizzling flush, and dyspepsia, in line with labeling.
Labeling warns that elacestrant “could trigger hypercholesterolemia and hypertriglyceridemia. Monitor lipid profile previous to beginning therapy and periodically thereafter.”
The beneficial elacestrant dose is the trial dose, 345 mg orally with meals as soon as every day till illness development or unacceptable toxicity.