Elacestrant in Women with Estrogen Receptor–Positive and HER2-Negative Early Breast Cancer: Results from the Preoperative Window-of-Opportunity ELIPSE Trial
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| Titel: | Elacestrant in Women with Estrogen Receptor–Positive and HER2-Negative Early Breast Cancer: Results from the Preoperative Window-of-Opportunity ELIPSE Trial |
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| Autoren: | Maria Vidal, Claudette Falato, Tomás Pascual, Rodrigo Sanchez-Bayona, Montserrat Muñoz-Mateu, Isaac Cebrecos, Xavier Gonzalez-Farré, Tomás Cortadellas, Mireia Margelí Vila, Miguel A. Luna, Christian Siso, Kepa Amillano, Patricia Galván, Milana A. Bergamino, Juan M. Ferrero-Cafiero, Fernando Salvador, Alejandra Espinosa Guerrero, Laia Pare, Esther Sanfeliu, Aleix Prat, Meritxell Bellet |
| Quelle: | Clin Cancer Res |
| Verlagsinformationen: | American Association for Cancer Research (AACR), 2025. |
| Publikationsjahr: | 2025 |
| Schlagwörter: | Treatment Outcome, Receptors, Estrogen, Receptor, ErbB-2, Biomarkers, Tumor, Humans, Clinical Trials: Targeted Therapy, Female, Breast Neoplasms, Middle Aged, Aged, Neoplasm Staging |
| Beschreibung: | Purpose: Elacestrant has shown significantly prolonged progression-free survival compared with standard-of-care endocrine therapy in estrogen receptor–positive (ER-positive), HER2-negative metastatic breast cancer, whereas potential benefit in early-stage disease requires further exploration. The SOLTI-ELIPSE window-of-opportunity trial investigated the biological changes induced by a short course of preoperative elacestrant in postmenopausal women with early breast cancer. Patients and Methods: Eligible patients with untreated T1c (≥1.5 cm)-T3, N0, ER-positive/HER2-negative breast cancer with locally assessed Ki67 ≥10% received elacestrant at a daily dose of 345 mg for 4 weeks. The primary efficacy endpoint was complete cell cycle arrest, defined as Ki67 ≤2.7%, on day 28. Results: Overall, 22 patients were evaluable for the primary endpoint. Elacestrant was associated with a complete cell cycle arrest rate of 27.3% and a statistically significant Ki67 geometric mean change of −52.9% (P = 0.007; 95% confidence interval, −67.4 to −32.1). Notably, the treatment with elacestrant led to a shift toward a more endocrine-sensitive and less proliferative tumor phenotype based on PAM50-based gene signatures. Elacestrant increased the expression of immune-response genes (GZMB, CD4, and CD8A) and suppressed proliferation and estrogen-signaling genes (MKI67, ESR1, and AR). These biological changes were independent of the levels of Ki67 suppression on day 28. The most common adverse events were grade 1 anemia (21.7%), hot flushes (8.7%), constipation (8.7%), and abdominal pain (8.7%). One patient experienced a grade 3 cutaneous rash, leading to treatment discontinuation. No other serious adverse events were reported. Conclusions: Preoperative treatment with elacestrant in early breast cancer demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting. |
| Publikationsart: | Article Other literature type |
| Sprache: | English |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-24-2460 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/39820652 |
| Rights: | CC BY NC ND URL: http://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) license. |
| Dokumentencode: | edsair.doi.dedup.....0828fb5d52bb003b1c2dbc7404e01f4a |
| Datenbank: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | Purpose: Elacestrant has shown significantly prolonged progression-free survival compared with standard-of-care endocrine therapy in estrogen receptor–positive (ER-positive), HER2-negative metastatic breast cancer, whereas potential benefit in early-stage disease requires further exploration. The SOLTI-ELIPSE window-of-opportunity trial investigated the biological changes induced by a short course of preoperative elacestrant in postmenopausal women with early breast cancer. Patients and Methods: Eligible patients with untreated T1c (≥1.5 cm)-T3, N0, ER-positive/HER2-negative breast cancer with locally assessed Ki67 ≥10% received elacestrant at a daily dose of 345 mg for 4 weeks. The primary efficacy endpoint was complete cell cycle arrest, defined as Ki67 ≤2.7%, on day 28. Results: Overall, 22 patients were evaluable for the primary endpoint. Elacestrant was associated with a complete cell cycle arrest rate of 27.3% and a statistically significant Ki67 geometric mean change of −52.9% (P = 0.007; 95% confidence interval, −67.4 to −32.1). Notably, the treatment with elacestrant led to a shift toward a more endocrine-sensitive and less proliferative tumor phenotype based on PAM50-based gene signatures. Elacestrant increased the expression of immune-response genes (GZMB, CD4, and CD8A) and suppressed proliferation and estrogen-signaling genes (MKI67, ESR1, and AR). These biological changes were independent of the levels of Ki67 suppression on day 28. The most common adverse events were grade 1 anemia (21.7%), hot flushes (8.7%), constipation (8.7%), and abdominal pain (8.7%). One patient experienced a grade 3 cutaneous rash, leading to treatment discontinuation. No other serious adverse events were reported. Conclusions: Preoperative treatment with elacestrant in early breast cancer demonstrated relevant biological and molecular responses and exhibited a manageable safety profile. These findings support further investigation of elacestrant in the early setting. |
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| ISSN: | 15573265 10780432 |
| DOI: | 10.1158/1078-0432.ccr-24-2460 |