Abstract PD13-01: PD13-01 Elacestrant in postmenopausal women with estrogen receptor positive and HER2-negative early breast cancer: primary efficacy and safety analysis of the preoperative, window of opportunity SOLTI-1905-ELIPSE trial
Authors: Vidal Maria , Pascual Tomás , Falato Claudette , Sanchez-Bayona Rodrigo , Muñoz Montserrat , Cerbrecos Isaac , Gonzalez-Farré Xavier , Cortadellas Tomás , Margelí Mireia , Luna Miguel Angel , Siso Christian , Amillano Kepa , Galván Patricia , Salvador Fernando , Espinosa Alejandra , Paré Laia , Sanfeliu Esther , Prat Aleix , Ezquerra Meritxell Bellet 
Published: March 2023

Abstract
Introduction Elacestrant is the first oral, non-steroidal, selective estrogen receptor degrader (SERD) to demonstrate improved efficacy compared to standard of care endocrine treatment, with greater relative benefit in ESR1-mutated tumors, and manageable safety profile in pretreated patients with metastatic breast cancer (BC) (Bidard F.C., JCO 2022). SOLTI ELIPSE trial (NCT04797728) is a prospective, multicenter, window of opportunity trial designed to assess whether a short-course of preoperative elacestrant may suppress tumor proliferation in postmenopausal women with estrogen receptor positive (ER+)/HER2-negative early BC (Vidal M., SABCS 2021). Here, we present the results of the primary efficacy and safety study analysis. Methods Eligible patients with operable, untreated ER+/HER2-negative BC that were T1c (≥1.5 cm)-T3 by ultrasound, clinically or radiologically N0 and had a locally assessed Ki67 ≥10%, received elacestrant 400 mg once a day continuously for a total of 4 weeks. At the study treatment completion, patients were treated according to local practice. Centralized assessment of post-treatment (D28) Ki67 from surgical specimen or tumor biopsy was required for the primary endpoint evaluation. Primary efficacy endpoint was complete cell cycle arrest (CCCA), defined as Ki67≤2.7%, at D28. Ki67 geometric relative change, variation in tumor infiltrating lymphocytes (TILs), switch in PAM50 subtypes and differential expression of 192 genes from baseline (D1) to D28 was also explored. Adverse events (AEs) were graded according to CTCAE v5.0. Results Between April 2021 and February 2022, 24 patients were enrolled and 22 were evaluable for the primary endpoint. Baseline characteristics were: mean age 69 years (range 50-81); ductal histology 74%; T1c 61%; T2 39%; grade 1-2 83%; median local Ki67 20% (10-70). Baseline PAM50 subtypes distribution was: Luminal A (n=12), Luminal B (n=8), Basal-like (n=1), Normal-like (n=1). At D28, CCCA was achieved in the 27% (n=6) of the patients. Fourteen patients (64%) had D28 Ki67 ≤10%. Paired centralized Ki67 was available in 19 patients. A statistically significant 41% (95% CI, -24 to -58) Ki67 relative reduction (rr) from D1 was observed (p=0.007). CCCA rate was 31% and 17% in patients with D1 Ki67 &lt; 20% (n=13) and D1 Ki67 ≥20% (n=6), respectively. Ki67 varied consistently in both Ki67 &lt; 20% (rr=-38%; 95% CI, -16 to -60) and Ki67 ≥20% (rr=-46%; 95% CI, -20 to -72) groups. Overall, elacestrant was associated with a shift towards a more endocrine sensitive and less proliferative phenotype based on PAM50 gene signatures. CCCA occurred in 45% of Luminal A tumors, whereas no CCCA was observed among Luminal B tumors. Levels of TILs were significantly higher at D28 (mean difference, +3.73; p=0.004). Elacestrant induced high expression of immune-response genes including IGJ, GZMB, CD4, CD8a and suppressed proliferation (e.g., UBE2T, MYBL2, BIRC5, MK67) and estrogen-signaling (e.g., ESR1, PGR, CCND1, BRCA2) genes (false discovery rate 5%). These changes in gene expression were observed both in tumors with D28 Ki67≤2.7% and in those with D28 Ki67 &gt;10%. Overall, 87% of the patients reported any grade AEs. Treatment-related AE occurred in 1 patient (grade 3 cutaneous rash) and led to treatment discontinuation. Most frequently reported AEs (all grade 1) were hot flush (n=6), dyspepsia (n=2), anemia (n=2) and constipation (n=2). No serious AEs were reported. Conclusions In untreated ER+/HER2-negative early BC a short-course preoperative treatment with elacestrant was associated with relevant biological and molecular response and with manageable safety profile. Globally, these findings support further exploration of this highly potent, novel oral SERD in early BC.
Citation Format: Maria Vidal, Tomás Pascual, Claudette Falato, Rodrigo Sanchez-Bayona, Montserrat Muñoz, Isaac Cerbrecos, Xavier Gonzalez-Farré, Tomás Cortadellas, Mireia Margelí, Miguel Angel Luna, Christian Siso, Kepa Amillano, Patricia Galván, Fernando Salvador, Alejandra Espinosa, Laia Paré, Esther Sanfeliu, Aleix Prat, Meritxell Bellet Ezquerra. PD13-01 Elacestrant in postmenopausal women with estrogen receptor positive and HER2-negative early breast cancer: primary efficacy and safety analysis of the preoperative, window of opportunity SOLTI-1905-ELIPSE trial [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr PD13-01.