Elacestrant Bests Standard of Care in PFS in ER Positive/HER2-Negative Metastatic Breast Cancer

Patients with ER-positive/HER-2 negative metastatic breast cancer who had been previously treated with CDK4/6 inhibitors had an increased progression-free survival (PFS) when treated with elacestrant compared to standard-of-care endocrine therapy, particularly if they had an ESR1 mutation, according to findings from the phase 3 EMERALD trial (NCT03778931).

These results, which were presented at the 2022 San Antonio Breast Cancer Symposium (SABCS), also demonstrated that the length of prior treatment with CDK4/6 inhibitors was associated with longer PFS.

“Most of (the) benefit is in the ESR1-mutated tumors,” explained Virginia Kaklamani, MD from The University of Texas Health Sciences Center in San Antonio, in a presentation of this data. “ESR1 mutation status will be important.”

Kaklamani explained that the trial enrolled men and postmenopausal women from 17 different countries with advanced or metastatic ER-positive/HER-negative breast cancer. The patients were randomized to receive either 400 mg of elacestrant daily or standard-of-care endocrine therapy consisting of either fulvestrant (Faslodex), anastrozole (Arimidex), letrozole (Femara) or exemestane (Aromasin) (SOC).

A total of 233 women and 6 men were given elacestrant and 238 women and 1 man were given SOC. The patients in the elacestrant arm ranged from 24 to 89 years old, with a median age of 63 years. The patients in the SOC arm ranged from 32 to 83 years old, with a median age of 63 years. Fourty-eight percent of the patients in the elacestrant arm had an ESR1 mutation (n=115) while 47% of the patients in the SOC group had an ESR1 mutation (n=113).

Among patients who had completed at least six months of treatment with CDK4/6 inhibitors (87.5% of trial participants), there was a 31.2% increase in PFS for patients who were given elacestrant compared to SOC (HR, 0.688; 95% CI, 0.535-0.884). The median PFS for patients in this group was 2.79 months (95% CI, 1.94-3.78) in the elacestrant arm and 1.91 months (95% CI, 1.87-2.14) in the SOC arm.

Among patients who had undergone at least 12 months of treatment with CDK4/6 inhibitors (66.7%), there was a 38.7% increase in PFS for patients who were given elacestrant compared to SOC (HR, .613). The median PFS for patients in this group was 3.78and 1.91 months in the elacestrant and SOC arms, respectively.

Among patients who had undergone at least 18 months of treatment with CDK4/6 inhibitors (46.7%), there was a 29.7% increase in PFS for patients who were given elacestrant compared to SOC (HR, .703). Median PFS for patients in this group was 5.45 months in the elacestrant arm, and 3.29 in the SOC arm.

At 12 months, the median PFS in the elacestrant arm was 3.78 months vs 1.91 months in the SOC arm (HR, 0.613; 95% CI, 0.453-0.828), and at 18 months it was 5.45 months (95% CI, 2.33-8.61) vs 3.29 months (95% CI, 1.87-3.71; HR, 0.703; 95% CI, 0.482-1.019).

Those with an ESR1 mutation had a median PFS at 6 months of 4.14 months (95% CI, 2.20-7.79) in the elacestrant arm vs 1.87 months (95% CI, 1.87-3.29) in the SOC arm (HR, 0.517; 95% CI, 0.361-0.738).

Among patients with an ESR1 mutation and who underwent at least six months of treatment with CDK4/6 inhibitors (92.3% of all participants with the mutation), there was a 48.3% increase in PFS for patients who were given elacestrant compared to SOC (HR, .517). The median PFS for patients in this group was 4.14 months for patients who were treated with elacestrant while it was 1.87 months for patients treated with SOC.

For patients with ESR1-mutant disease who underwent 12 months or more of CDK4/6 inhibitor treatment, (71.6%), there was a 59% increase in PFS for patients who were given elacestrant compared to SOC (HR, .410). The median PFS for patients in this group was 8.61 months for patients who were treated with elacestrant and 1.91 months for patients treated with SOC.

Among patients with an ESR1 mutation who had received at least 18 months of treatment with CDK4/6 inhibitors (50.0%), there was a 53.4% increase in PFS for patients who were given elacestrant compared to SOC (HR, .466). Median PFS for patients in this group was 8.61 and 2.10 months for patients in the elacestrant and SOC arms, respectively.

According to Kaklamani, only 3.4% of the patients who received elacestrant and .9 % of patients who received SOC needed to discontinue the trial due to treatment-related adverse effects (TRAE). Grade 3 nausea occurred in 2.5% of patients in the elacestrant arm vs 0% in the SOC. There were no deaths assessed relating to TRAEs in either arm.

Kaklamani claimed that this data shows that elacestrant can become an important oral endocrine monotherapy agent in the second- and third-line setting as an alternative to other therapies, which may cause other toxicities.

“If you look at the outcomes, not just in this trial but of others in patients whose CDK4/6 (inhibitor therapy) is less than six months” Kaklamani explained, “it gives you the idea that there are resistant tumors that need to move on to either chemotherapy or potentially combination endocrine therapy, but those treatments are toxic to our patients…”

In her presentation, Kaklamani stressed that this data reflects a need for patients to find out if their tumors are endocrine-resistant or not.

“Hopefully (with this trial) we'll have options for those patients,” she concluded.

Reference

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: 2022 San Antonio Breast Cancer Symposium; December 6-10, 2022; San Antonio, TX. Abstract GS3-01.