EU’s CHMP Recommends Elacestrant Approval In Advanced Breast Cancer

The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has taken a positive opinion toward the approval of elacestrant (Orserdu) monotherapy for the treatment of postmenopausal patients with estrogen receptor (ER)-positive, HER2-negative, ESR1-mutated, locally advanced or metastatic breast cancer who had progression on at least 1 prior line of endocrine therapy, according to a press release from the Menarini Group.¹

Elacestrant was previously approved by the FDA for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer in January 2023.

The opinion is based on findings from the phase 3 EMERALD trial (NCT03778931), in which elacestrant achieved a significant improvement in progression-free survival (PFS) vs standard-of-care (SOC) endocrine monotherapy. Among patients with ESR1 mutations, the median PFS was 3.8 months with elacestrant vs 1.9 months with standard of care, and the experimental agent reduced the risk of progression or death by 45% (HR, 0.55; 95% CI, 0.39-0.77).

A post-hoc subgroup analysis of the EMERALD trial, presented at the 2022 San Antonio Breast Cancer Symposium (SABCS), demonstrated a positive association between the duration of prior CDK4/6 inhibitor treatment and longer PFS with elacestrant; this association did not occur with standard of care therapy.² Patients with ESR1 mutations who received a CDK4/6 inhibitor for 12 or more months prior to randomization had a median PFS of 8.6 months with elacestrant, as compared with 1.9 months with standard of care. There was a 59% reduction in the risk of progression or death (HR, 0.41; 95% CI, 0.26-0.63) with elacestrant.

The European Commission will review the CHMP opinion and determine whether to grant marketing authorization for the agent in the European Union.

“As an oncologist, it is remarkable that we are on the cusp of having the first treatment option for patients with advanced or metastatic ER-positive, HER2-negative breast cancer harboring ESR1 mutations, which occur in up to 40% of patients in the metastatic setting,” Giuseppe Curigliano, MD, PhD, professor of medical oncology at the University of Milan and the head of the Division of Early Drug Development at the European Institute of Oncology, said in the press release.¹ “Elacestrant has demonstrated efficacy and a manageable safety profile, underscoring the potential benefit this therapy may soon bring to the patients we care for, and to the broader oncology community.”

The randomized, open label EMERALD trial included 478 patients and assessed elacestrant in the second- and third-line settings. The primary end points were PFS in both the overall population and among patients with ESR1-mutated disease.

The safety profile of elacestrant in the EMERALD trial was found to be comparable with previous reports. The most frequent adverse effects of grade 3 or higher were nausea (2.7%), increased aspartate aminotransferase (2.7%), increased alanine transaminase (2.3%), anemia (2%), back pain (2%), and bone pain (2%).

“Elacestrant, if approved, will also provide a convenient daily oral treatment,” Elcin Barker Ergun, chief executive officer of the Menarini Group, said in the press release.¹ “We are proud of today’s positive CHMP opinion as it reflects our commitment to developing innovative solutions that address the greatest unmet needs in cancer treatment, and brings us one step closer to providing an important new option to the patients and families impacted by ESR1-mutated, ER-positive, HER2-negative metastatic breast cancer.”

Elacestrant was previously approved by the FDA for this patient population in January 2023.³

References

1. Menarini Group receives positive CHMP opinion recommending EC approval of ORSERDU® (elacestrant) for the treatment of patients with ER+, HER2- locally advanced or metastatic breast cancer with an activating ESR1 mutation. News Release. Menarini Group. July 21, 2023. Accessed July 21, 2023. https://bit.ly/3QcifTP
2. 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.
3. FDA approves elacestrant for ER-positive, HER2-negative, ESR1-mutated advanced or metastatic breast cancer. News release. FDA. January 27, 2023. Accessed July 21, 2023. bit.ly/3kQrxHq