ѻý

MedpageToday
ASCO > Breast Cancer

FDA Approval Summary: Elacestrant for ER–Positive, HER 2–Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer

<ѻý class="mpt-content-deck">– An ASCO Reading Room selection
Mirat Shah, MD, Hima Lingam, MD, Xin Gao, PhD, Haley Gittleman, PhD7, Mallorie H. Fiero, PhD, Danielle Krol, MD, Nikolett Biel, PhD, Tiffany K. Ricks, PhD, Wentao Fu, PhD, Salaheldin Hamed, PhD, Fang Li, PhD, Jillian (Jielin) Sun, PhD, Jianghong Fan, PhD, Robert Schuck, PharmD, PhD, Manuela Grimstein, PhD, Liuya Tang, PhD, Shyam Kalavar, PhD, Abdelrahmman Abukhdeir, PhD, Anand Pathak, MD, PhD, MPH, Soma Ghosh, PhD, Ilynn Bulatao, MD, PhD, Amy Tilley, BBA, William F. Pierce, PharmD, MPH, Bronwyn D. Mixter, Shenghui Tang, PhD, Richard Pazdur, MD, Paul Kluetz, MD, and Laleh Amiri-Kordestani, MD
Journal of Clinical Oncology

This Reading Room is a collaboration between ѻý® and:

Medpage Today
Below is the abstract of the article.
Read the full article PDF by clicking here
or on the link below.

Purpose

The U.S. Food and Drug Administration approved elacestrant for the treatment of postmenopausal women or adult men with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), estrogen receptor 1 (ESR1)–mutated advanced or metastatic breast cancer with disease progression after at least one line of endocrine therapy (ET).

Patients and Methods

Approval was based on EMERALD (Study RAD1901-308), a randomized, open-label, active-controlled, multicenter trial in 478 patients with ER+, HER2– advanced or metastatic breast cancer, including 228 patients with ESR1 mutations. Patients were randomly assigned (1:1) to receive either elacestrant 345 mg orally once daily (n = 239) or investigator's choice of ET (n = 239).

Results

In the ESR1-mut subgroup, EMERALD demonstrated a statistically significant improvement in progression-free survival (PFS) by blinded independent central review assessment (n = 228, hazard ratio [HR] 0.55, 95% CI 0.39-0.77, P value=0.0005). Although the overall survival (OS) end point was not met, there was no trend toward a potential OS detriment (HR 0.90, 95% CI 0.63-1.30) in the ESR1-mut subgroup. PFS also reached statistical significance in the intention-to-treat (ITT) population (n = 478; HR 0.70, 95% CI 0.55-0.88]; P value=0.0018). However, improvement in PFS in the ITT population was primarily attributed to results from patients in the ESR1-mut subgroup. More patients who received elacestrant experienced nausea, vomiting, and dyslipidemia.

Conclusion

The approval of elacestrant in ER+, HER2– advanced or metastatic breast cancer was restricted to patients with ESR1 mutations. Benefit-risk assessment in the ESR1-mut subgroup was favorable on the basis of a statistically significant improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in OS. By contrast, the benefit-risk assessment in patients without ESR1 mutations was not favorable. Elacestrant is the first oral estrogen receptor antagonist to receive FDA approval for patients with ESR1 mutations.

Read an interview about the FDA approval summary special article here.

Read the full article

FDA Approval Summary: Elacestrant for ER–Positive, HER 2–Negative, ESR1-Mutated Advanced or Metastatic Breast Cancer

Primary Source

Journal of Clinical Oncology

Source Reference:

ASCO Publications Corner

ASCO Publications Corner