Skip to content
Bending the Curve Trial by Trial
?

EMERALD

Needs review

Elacestrant (oral selective estrogen receptor degrader) versus standard endocrine therapy for estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: results from the randomized phase III EMERALD trial

Phase 3N = 477NCT03778931

Population
ER-positive, HER2-negative advanced breast cancer after one or two lines of endocrine therapy, with prior CDK4/6 inhibitor and no more than one chemotherapy; ESR1 mutation detected in 47.8%
Design
Randomized, open-label phase III trial of elacestrant 400 mg orally once daily versus standard-of-care endocrine monotherapy (fulvestrant or an aromatase inhibitor); primary endpoints PFS by blinded independent central review in all patients and in patients with detectable ESR1 mutations
Primary endpoint
PFS
Arms
  • Elacestrant (experimental, n = 239): Elacestrant 400 mg orally once daily
  • Standard-of-care endocrine therapy (control, n = 238): Investigator's choice endocrine monotherapy (fulvestrant or aromatase inhibitor)
People
Bidard FC
PFSHR 0.70 (95% CI 0.55–0.88)PFSHR 0.55 (95% CI 0.39–0.77)Δ 6-month PFS+13.9 pointsΔ 6-month PFS+21.7 pointsPFSHR 0.55Δ median PFS+1.9 months
Show the numbers
Results reported for EMERALD
EndpointAnalysisElacestrantStandard-of-care endocrine therapyEffect
PFSprimaryBidard 2022——HR 0.70 (95% CI 0.55–0.88)P=.002Blinded independent central review.
PFSESR1-mutated (detectable ESR1 mutation)primaryBidard 2022——HR 0.55 (95% CI 0.39–0.77)P=.0005Blinded independent central review.
PFSprimaryBidard 202234.3% at 6 mo (27.2–41.5%); 22.3% at 12 mo (15.2–29.4%)20.4% at 6 mo (14.1–26.7%); 9.4% at 12 mo (4.0–14.8%)Landmark analysis used by the authors because the curves show an early drop in both arms; median PFS alone can mislead (authors' statement).
PFSESR1-mutated (detectable ESR1 mutation)primaryBidard 202240.8% at 6 mo (30.1–51.4%); 26.8% at 12 mo (16.2–37.4%)19.1% at 6 mo (10.5–27.8%); 8.2% at 12 mo (1.3–15.1%)—
PFSESR1-mutated (228 patients per FDA page)primarySource 2023median 3.8 monthsmedian 1.9 monthsHR 0.55Medians are not in the journal abstract; they are on the FDA page and in the paper's Discussion (full text). The hazard ratio is the abstract's.
OSinterimBidard 2022——HR 0.75 (95% CI 0.54–1.04)P=.08Interim analysis; not statistically significant against the allocated alpha.
OSESR1-mutated (detectable ESR1 mutation)interimBidard 2022——HR 0.59 (95% CI 0.36–0.96)P=.03Interim analysis, labelled nonsignificant by the authors.
Results reported for EMERALD
EndpointAnalysisElacestrantStandard-of-care endocrine therapyEffect
PFSprimaryBidard 2022——HR 0.70 (95% CI 0.55–0.88)P=.002Blinded independent central review.
PFSESR1-mutated (detectable ESR1 mutation)primaryBidard 2022——HR 0.55 (95% CI 0.39–0.77)P=.0005Blinded independent central review.
PFSprimaryBidard 202234.3% at 6 mo (27.2–41.5%); 22.3% at 12 mo (15.2–29.4%)20.4% at 6 mo (14.1–26.7%); 9.4% at 12 mo (4.0–14.8%)Landmark analysis used by the authors because the curves show an early drop in both arms; median PFS alone can mislead (authors' statement).
PFSESR1-mutated (detectable ESR1 mutation)primaryBidard 202240.8% at 6 mo (30.1–51.4%); 26.8% at 12 mo (16.2–37.4%)19.1% at 6 mo (10.5–27.8%); 8.2% at 12 mo (1.3–15.1%)—
PFSESR1-mutated (228 patients per FDA page)primarySource 2023median 3.8 monthsmedian 1.9 monthsHR 0.55Medians are not in the journal abstract; they are on the FDA page and in the paper's Discussion (full text). The hazard ratio is the abstract's.
OSinterimBidard 2022——HR 0.75 (95% CI 0.54–1.04)P=.08Interim analysis; not statistically significant against the allocated alpha.
OSESR1-mutated (detectable ESR1 mutation)interimBidard 2022——HR 0.59 (95% CI 0.36–0.96)P=.03Interim analysis, labelled nonsignificant by the authors.
Hazard ratio (95% CI) by endpoint. Values below 1 favour the experimental arm.
PFSPFSOSOS0.512◀ experimentalcontrol ▶
Data table
EndpointHR95% CI
PFS0.70.55–0.88
PFS0.550.39–0.77
OS0.750.54–1.04
OS0.590.36–0.96
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%024681012Months (modelled)
  • Elacestrant (experimental)
  • Standard-of-care endocrine therapy (control)
Data table (modelled values)
MonthsElacestrantStandard-of-care endocrine therapy
0100.0%100.0%
363.2%54.3%
634.3%20.4%
1024.4%11.0%
1322.3%9.4%
Illustrative — modelled from reported values, not trial data. PFS, primary.
0%25%50%75%100%024681012Months (modelled)
  • Elacestrant (experimental)
  • Standard-of-care endocrine therapy (control)
Data table (modelled values)
MonthsElacestrantStandard-of-care endocrine therapy
0100.0%100.0%
367.6%53.4%
640.8%19.1%
1029.8%9.8%
1326.8%8.2%
Primary publication: Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022;40(28):3246-3256. PubMedDOI

Appears in

Sources

  1. Bidard FC, Kaklamani VG, Neven P, Streich G, Montero AJ, Forget F, et al. Elacestrant (oral selective estrogen receptor degrader) Versus Standard Endocrine Therapy for Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: Results From the Randomized Phase III EMERALD Trial. J Clin Oncol. 2022;40(28):3246-3256.

    PubMedDOI

  2. US Food and Drug Administration. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. 27 January 2023.

    Source