September 30, 2023

The US Meals and Drug Administration accredited elacestrant (Orserdu, Stemline Therapeutics, Inc) for postmenopausal ladies or males with ER-positive, HER2-negative, ESR1-mutated superior or metastatic breast most cancers that progressed on no less than one line of endocrine remedy.

The company additionally accredited the Guardant360 CDx assay as a companion diagnostic to determine breast most cancers sufferers who meet the therapy necessities, in accordance with the company’s press release asserting the approval.

The novel oral selective estrogen receptor degrader was accredited primarily based on the section 3 EMERALD trial, which included 478 postmenopausal ladies and men 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. Members might even have had one prior line of chemotherapy within the superior or metastatic setting.

Members have been randomized 1:1 to both elacestrant 345 mg orally as soon as day by 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.

Truthful Comparability?

In a Medscape Medical Information story revealed in June, specialists raised issues concerning the adequacy of the “customary of care” management arm in EMERALD, significantly that single brokers have been used at a time when mixture remedy is changing into extra frequent.

“The expression ‘customary of care’ is utilized generously, because the management arm is restricted” to single brokers and no mixtures, which “might 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 an alternative of single brokers — “is more and more getting used because the second-line [standard of care] therapy.”

Nevertheless, the aim of the examine “was to match a novel endocrine remedy vs at present out there 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 Needed

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, belly ache, sizzling flush, and dyspepsia, in accordance with labeling.

Labeling warns that elacestrant “might 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 day by day till illness development or unacceptable toxicity.

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