Clinical and Genomic Factors Associated with Elacestrant Outcomes in ESR1- Mutant Metastatic Breast Cancer

作者：Maxwell Roger Lloyd, Caroline M. Weipert, Azka Ali, Sheila R. Solomon, Jayati Saha, Marla D. Lipsyc-Sharf, Erika Paige Hamilton, Kevin M. Kalinsky, Adam Brufsky, Aditya Bardia, Nicole J. Zhang, Seth Andrew Wander · 发表于：Clinical Cancer Research · 年份：2025 · DOI：10.1158/1078-0432.ccr-25-3033 · 被引用次数：8 · 研究领域：Advanced Breast Cancer Therapies、Estrogen and related hormone effects、PI3K/AKT/mTOR signaling in cancer

PURPOSE: ESR1 mutations mediate resistance to antiestrogen therapy in hormone receptor-positive metastatic breast cancer (MBC). Elacestrant, an oral selective estrogen receptor degrader, improves progression-free survival over standard endocrine therapy in ESR1-mutant MBC. We assessed real-world elacestrant use and clinical-genomic factors associated with outcomes. EXPERIMENTAL DESIGN: This study used the GuardantINFORM database, linking >42,000 real-world breast cancer cases with sequencing and claims data. We included patients with activating ESR1 mutations detected <6 months before elacestrant initiation (January 2023-March 2024). Outcomes of time-to-treatment-discontinuation, time-to-next-treatment (TTNT), and overall survival were estimated with Kaplan-Meier and Cox regression analysis, adjusting for clinical variables. RESULTS: We identified 756 patients (76% with prior cyclin-dependent kinase-4/6 inhibitor and 38% with prior chemotherapy exposure), and 742 (98.2%) were evaluable for outcomes. The median TTNT was 6.4 months, and the time-to-treatment-discontinuation was 4.6 months. In those with ≤1 prior lines of metastatic therapy, the TTNT was 8.8 months, compared with 6.0 months in the third-line setting. Prior fulvestrant exposure trended toward shorter treatment duration (hazard ratio, 1.19; 95% confidence interval, 0.91-1.56). Higher ESR1 polyclonality (≥4 alterations; 11% of patients) correlated with a shorter TTNT of 5.2 months (hazard ratio, 1.44; 95% confidenc...