Elacestrant in ESR1-mutant, endocrine-responsive metastatic breast cancer: should health authorities consider post hoc data to inform priority access?

Abstract

For patients with hormone receptor-positive/human epidermal growth factor receptor 2 (HER2)-negative (HR+/HER2-) metastatic breast cancer (mBC) progressed on first-line endocrine therapy plus a cyclin-dependent kinase 4 and 6 inhibitor (CDK4/6i), fulvestrant, a selective estrogen receptor degrader (SERD) administered intramuscularly, represented the only monotherapy option until the approval of elacestrant. This oral SERD has been approved for patients with ESR1-mutant HR+/HER2- mBC by the European Medicines Agency, the Food and Drug Administration, and the UK Medicines and Healthcare products Regulatory Agency, according to the results of the randomized phase III EMERALD trial, which demonstrated elacestrant superiority over standard endocrine monotherapy. Consequently, elacestrant has been incorporated in the European Society for Medical Oncology and American Society of Clinical Oncology guidelines. However, in Europe, the access to this recommended drug depends on the decision of the National Health Authorities of each state. In this communication, we describe the main results and implications of the EMERALD trial, in the context of the biomarker-driven algorithm for patients with HR+/HER2- mBC progressed on CDK4/6i, and conclude that a subgroup of patients with ESR1-mutant tumors and specific clinical features can really derive a clinically meaningful benefit from elacestrant, sparing access to more toxic combination approaches and preserving the quality of life.

Keywords: elacestrant; hormone receptor-positive/HER2-negative breast cancer; metastatic breast cancer.

Figure 1

Systemictreatment options for postmenopausal women with ER-positive and HER2-negative locally advanced or metastatic breast cancer. a, altered; ADC, antibody–drug conjugate; BRCA, breast cancer gene; CDK4/6, cyclin-dependent kinase 4 and 6; ER, estrogen receptor; ESR1, estrogen receptor 1; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; m, mutation; PARP, poly (ADP-ribose) polymerase; PD, progressive disease; PFS, progression-free survival; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; SoC, standard of care.^aConsider previous therapies, disease aggressiveness, extent and organ function, and toxicity profile. ^bFulvestrant, aromatase inhibitors, and tamoxifen are routinely and sequentially used in multiple lines. ^cNo controlled studies conducted in post-CDK4/6 inhibitor therapy. ^dChemotherapy preferred option in patients with imminent organ failure, after at least two lines of ET, and/or in patients with limited PFS after CDK4/6 inhibitor. Chemotherapy could also be an alternative to PARP inhibitor therapy. a, altered; ADC, antibody–drug conjugate; BRCA, breast cancer gene; CDK4/6, cyclin-dependent kinase 4 and 6; ER, estrogen receptor; ESR1, estrogen receptor 1; ET, endocrine therapy; HER2, human epidermal growth factor receptor 2; m, mutation; PARP, poly (ADP-ribose) polymerase; PD, progressive disease; PFS, progression-free survival; PIK3CA, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; SoC, standard of care.