Abstract PS1-10-06: Impact of prior fulvestrant use and endocrine therapy duration on real-world outcomes of elacestrant treatment in ER+/HER2- metastatic breast cancer

Abstract Background: Endocrine therapy (ET) combined with a CDK4/6 inhibitor (CDK4/6i) is the standard first-line treatment for patients (pts) with estrogen receptor-positive (ER+), HER2-negative (HER2-) metastatic breast cancer (mBC). However, many pts eventually develop endocrine resistance, often driven by acquired ESR1 mutations (ESR1m). Elacestrant is the first oral selective estrogen receptor degrader approved for pts with ESR1-mutated ER+/HER2- mBC. Approval was based on the phase III EMERALD trial, which demonstrated significantly improved progression-free survival (PFS) compared to standard-of-care ET in pts with ESR1m. Notably, ∼29% of pts received prior fulvestrant, and subgroup analyses showed a PFS benefit with elacestrant even in this subgroup. Exploratory analyses suggest that pts with longer disease control on prior ET + CDK4/6i may derive greater benefit from elacestrant. Despite these findings, real-world evidence on how prior ET exposure, including fulvestrant use and ET duration, impacts elacestrant outcomes is limited. This study assessed the association of prior fulvestrant use and prior ET duration with time to next treatment (TTNT) and real-world overall survival (rwOS) among pts who received elacestrant monotherapy. Methods: The IntegraConnect PrecisionQ de-identified electronic health record database, (3 million cancer pts, 500 care sites) was utilized to identify pts treated with elacestrant monotherapy between 1/27/2023 and 1/31/2025. All pts received ≥1 ET before elacestrant initiation. ESR1m was not assessed but assumed present. Pts were stratified by prior use of fulvestrant monotherapy, prior use of fulvestrant + CDK4/6i, and duration of prior ET (12 vs. ≥12 mo, ET could be other than fulvestrant). Kaplan-Meier survival curves were used to assess TTNT and rwOS across subgroups. Multivariable Cox proportional hazards regression was used to evaluate the association of prior fulvestrant use and ET duration with TTNT and rwOS, adjusting for clinical and demographic covariates including age at index date, race, ethnicity, Eastern Cooperative Oncology Group performance status, and metastatic line of therapy. Results: A total of 589 pts met study inclusion criteria: 77 pts (13%) received fulvestrant monotherapy previously, 294 (50%) received fulvestrant + CDK4/6i previously, and 329 (56%) had ≥12 mo duration of prior ET. No significant differences in TTNT or rwOS were observed by prior fulvestrant monotherapy (prior fulvestrant vs. no prior fulvestrant median TTNT, 6 vs. 5.3 mo; median rwOS, 18.3 vs. 17.3 mo) or CDK4/6i combination therapy (prior CDK4/6i + fulvestrant vs. no prior CDK4/6i + fulvestrant, median TTNT 5.2 vs. 5.7 mo; median rwOS, 18.3 vs. 17.3 mo). Pts with ≥12 mo of prior ET had significantly longer TTNT (6 vs. 4.6 mo, log-rank p0.001) and improved rwOS (23.0 vs. 13.8 mo; log-rank p0.001). In multivariable analyses, pts with ≥12 mo prior ET were 31% less likely to initiate a subsequent treatment (TTNT hazard ratio HR, 0.69; 95% confidence interval CI 0.56-0.85). The impact on rwOS was attenuated after adjustment (HR, 0.77; 95% CI, 0.58-1.03, p=0.079). Conclusions: In this real-world cohort of pts treated with elacestrant, prior fulvestrant use did not significantly impact clinical outcomes. However, longer duration of prior ET (≥12 mo) was associated with delayed TTNT, even after adjusting for key clinical factors. These findings are consistent with a post-hoc analysis from the EMERALD trial. Our real-world results further support the hypothesis that longer endocrine sensitivity may enrich for elacestrant-responsive disease and inform treatment sequencing decisions in clinical practice. Citation Format: S. Reddy, R. Choksi, V. Gorantla, F. Kudrik, D. Patt, S. Reganti, S. Rosenfeld, G. Cioffi, F. Yang, D. Parris, A. Rui, M. Gart, C. Wall, B. Wang, P. Varughese, J. Donegan, L. Morere, R. Geller, J. Scott, R. Mahtani. Impact of prior fulvestrant use and endocrine therapy duration on real-world outcomes of elacestrant treatment in ER+/HER2- metastatic breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-06.