that progressed on at least one line of endocrine therapy.
The agency also approved the Guardant360 CDx assay as a companion diagnostic to identify breast cancer patients who meet the treatment requirements, according to the agency’s press release announcing the approval.
The novel oral selective estrogen receptor degrader was approved based on the phase 3 EMERALD trial, which included 478 postmenopausal women and men with ER-positive, HER2-negative advanced or metastatic breast cancer, about half of whom had ESR1 mutations. Patients had progressed on one or two prior lines of endocrine therapy, including one containing a CDK4/6 inhibitor. Participants could also have had one prior line of chemotherapy in the advanced or metastatic setting.
Participants were randomized 1:1 to either elacestrant 345 mg orally once daily or investigator’s choice of endocrine therapy, which included fulvestrant or an aromatase inhibitor.
In the 228 patients (48%) with ESR1 mutations, median progression-free survival (PFS) was 3.8 months with elacestrant versus 1.9 months in the fulvestrant or aromatase inhibitor arm (hazard ratio, 0.55; P = .0005). Investigators observed no statistically significant PFS difference between the treatment arms in patients who didn’t have the mutation.
In June, experts raised concerns about the adequacy of the “standard of care” control arm in EMERALD, particularly that single agents were used at a time when combination therapy is becoming more common.
“The expression ‘standard of care’ is applied generously, as the control arm is restricted” to single agents and no combinations, which “may have led to a substandard” comparison group, Timothée Olivier, MD, Geneva University Hospital, and Vinay Prasad, MD, MPH, University of California, San Francisco, said in an editorial quoted in the piece.
EMERALD investigators acknowledged that there were issues with the control group, noting that in the “United States and Europe, combination therapy with fulvestrant” – instead of single agents – “is increasingly being used as the second-line [standard of care] treatment.”
However, the goal of the study “was to compare a novel endocrine therapy vs. currently available endocrine therapies,” not combination regimens, the investigators said.
Also, “the benefit of elacestrant over fulvestrant and AIs [aromatase inhibitors] in our monotherapy trial ... suggests that incorporating elacestrant as the preferred endocrine therapy backbone in future earlier-line combination studies is a promising strategy.”
Lipid monitoring necessary
The most common adverse events with elacestrant, occurring in 10% or more of patients, are musculoskeletal pain, nausea, increased cholesterol, increased AST, increased triglycerides, fatigue, decreased hemoglobin, vomiting, increased ALT, decreased sodium, increased creatinine, decreased appetite, diarrhea, headache, constipation, abdominal pain, hot flush, and dyspepsia, according to labeling.
Labeling warns that elacestrant “may cause hypercholesterolemia and hypertriglyceridemia. Monitor lipid profile prior to starting treatment and periodically thereafter.”
The recommended elacestrant dose is the trial dose, 345 mg orally with food once daily until disease progression or unacceptable toxicity.
A version of this article first appeared on Medscape.com.