The duration of prior treatment with a CDK4/6 inhibitor appears to impact the progression-free survival (PFS) benefit of elacestrant in patients with estrogen receptor (ER)-positive, HER2-negative, metastatic breast cancer, according to updated results from the EMERALD trial.
The trial showed that elacestrant improved PFS when compared with standard of care (SOC) in this patient population. Additionally, patients who had previously received a CDK4/6 inhibitor for a longer period of time had longer PFS when treated with elacestrant.
“These updated results demonstrate that monotherapy use of elacestrant is safe and significantly prolongs median PFS vs SOC and meaningfully extends landmark PFS rates,” said Virginia Kaklamani, MD, of UT Health San Antonio, when presenting the results at the San Antonio Breast Cancer Symposium 2022.
The phase 3 EMERALD trial (ClinicalTrials.gov Identifier: NCT03778931) enrolled men and postmenopausal women with ER-positive, HER2-negative metastatic breast cancer who had previously received endocrine therapy in combination with a CDK4/6 inhibitor.
The 478 patients were randomly assigned to receive elacestrant at 400 mg daily (n=239) or SOC (n=239) until disease progression or withdrawal. Patients in the SOC arm received investigator’s choice of fulvestrant, anastrozole, letrozole, or exemestane.
The median age was 63.0 years in both treatment arms. Most patients were women (97.5% in the elacestrant arm and 99.6% in the SOC arm), had visceral metastasis (68.2% and 71.1%, respectively), were chemotherapy-naïve (79.9% and 75.3%), and received 1 prior line of endocrine therapy (54.0% and 59.4%). A similar number of patients in each arm had ESR1 mutations (115 and 113, respectively).
The researchers found that elacestrant was associated with improved PFS compared with SOC for patients who received:
- At least 6 months of CDK4/6 inhibitor treatment, with a median PFS of 2.79 months and 1.91 months, respectively (hazard ratio [HR], 0.688; 95% CI, 0.535-0.884)
- At least 12 months of CDK4/6 inhibitor treatment, with a median PFS of 3.78 months and 1.91 months, respectively (HR, 0.613; 95% CI, 0.453-0.828)
- At least 18 months of CDK4/6 inhibitor treatment, with a median PFS of 5.45 months and 3.29 months, respectively (HR, 0.703; 95% CI, 0.482-1.019).
This effect was more pronounced in the subset of patients with ESR1 mutations, Dr Kaklamani noted. In this group, elacestrant was associated with improved PFS compared with SOC for patients who received:
- At least 6 months of CDK4/6 inhibitor treatment, with a median PFS of 4.14 months and 1.87 months, respectively (HR, 0.517; 95% CI, 0.361-0.738)
- At least 12 months of CDK4/6 inhibitor treatment, with a median PFS of 8.61 months and 1.91 months, respectively (HR, 0.410; 95% CI, 0.262-0.634)
- At least 18 months of CDK4/6 inhibitor treatment, with a median PFS of 8.61 months and 2.10 months, respectively (HR, 0.466; 95% CI, 0.270-0.791).
There were no grade 4 adverse events. Grade 3 nausea occurred in 2.5% of elacestrant recipients and 0.9% of SOC recipients. Dose reductions and discontinuations due to nausea occurred in 3 elacestrant recipients but none of the patients who received SOC.
No hematologic adverse events or sinus bradycardia events occurred, and no deaths were deemed related to treatment.
“Elacestrant can become an important oral antibody monotherapy in the second- and third-line treatment setting as an alternative to combination therapies that are associated with challenging safety profiles,” Dr Kaklamani said.
Disclosures: This research was supported by Stemline Therapeutics, Radius Health, and Menarini Group. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.
Bardia A, Bidard FC, Neven P, et al. EMERALD phase 3 trial of elacestrant versus standard of care endocrine therapy in patients with ER+/HER2- metastatic breast cancer: Updated results by duration of prior CDK4/6i in metastatic setting. Presented at SABCS 2022. December 6-10, 2022. Abstract GS3-01.