Orserdu (elacestrant)

P2, N=297, Recruiting, Kristina A. Fanucci | Not yet recruiting --> Recruiting

P1, N=240, Recruiting, Stemline Therapeutics, Inc. | Trial primary completion date: Oct 2025 --> Jun 2026

P2, N=24, Active, not recruiting, University of Miami | Recruiting --> Active, not recruiting | N=500 --> 24

With the growing integration of liquid biopsy technologies and molecular monitoring into clinical practice, dynamic treatment adaptation guided by real time molecular profiling is expected to refine therapy selection. Elacestrant is a benchmark in the shift toward individualized endocrine therapy in metastatic breast cancer, bridging molecular precision with clinical practicality.

P3, N=240, Active, not recruiting, MedSIR | Recruiting --> Active, not recruiting

P2, N=140, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Not yet recruiting --> Recruiting

The analysis commenced with elacestrant (2022) and fulvestrant (2004), concluding in the fourth quarter of 2024. For fulvestrant, increased vigilance is necessary regarding cancer metastasis and adverse events impacting the hematological and lymphatic systems. It is recommended that targeted monitoring be enhanced in clinical practice in accordance with the distinct characteristics of each drug.

P3, N=1520, Not yet recruiting, West German Study Group

Elacestrant demonstrated durable benefit in real-world clinical practice, particularly in earlier lines and in patients with prolonged prior ET exposure. Despite coexisting ESR1 and PI3K-pathway mutations, TTNT remained clinically meaningful, reinforcing the role of elacestrant in personalized ET sequencing strategies prior to chemotherapy, antibody-drug conjugates, or targeted combinations.

We demonstrated that CDD-1274 induced proteasomal degradation of ERα variants in breast cancer cell lines and caused Y537S ERα degradation more effectively than elacestrant in a palbociclib-resistant cell line. These findings establish that CDD-1274 potently blocks ligand-dependent and ligand-independent ER signaling in endocrine-resistant breast cancer cells and could be further optimized for developing a new class of ERα degraders for endocrine therapy-resistant breast cancer.

In ESR1-mutant MBC, elacestrant treatment durations support the routine use of elacestrant monotherapy in appropriately selected patients. For patients with concurrent ESR1 and PI3K-pathway mutations, single-agent activity was comparable to outcomes observed in phase III studies.

Importantly, ferroptosis inducers potentiated the effects of the selective estrogen receptor degraders fulvestrant and elacestrant, which are the standard of care for breast cancers carrying ESR1 mutations. These findings, validated both in preclinical models and in patient-derived material, identify a combinatory therapeutic approach in the setting of ET resistance and establish ACSL4 as an important biomarker to recognize ER+ breast cancers susceptible to ferroptosis induction.