Vidal Maria, Falato Claudette, Pascual Tomás, Sanchez-Bayona Rodrigo, Muñoz-Mateu Montserrat, Cebrecos Isaac, Gonzalez-Farré Xavier, Cortadellas Tomás, Margelí Vila Mireia, Luna Miguel A, Siso Christian, Amillano Kepa, Galván Patricia, Bergamino Milana A, Ferrero-Cafiero Juan M, Salvador Fernando, Espinosa Guerrero Alejandra, Pare Laia, Sanfeliu Esther, Prat Aleix, Bellet Meritxell
SOLTI Cancer Research Group, Barcelona, Spain.
Cancer Institute and Blood Disorders, Hospital Clinic de Barcelona, Barcelona, Spain.
Clin Cancer Res. 2025 Apr 1;31(7):1223-1232. doi: 10.1158/1078-0432.CCR-24-2460.
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.
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.
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.
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.
与雌激素受体阳性（ER阳性）、人表皮生长因子受体2阴性（HER2阴性）转移性乳腺癌的标准内分泌治疗相比，艾拉司群已显示出显著延长的无进展生存期，而其在早期疾病中的潜在益处需要进一步探索。SOLTI-ELIPSE机会窗试验研究了绝经后早期乳腺癌女性术前短期使用艾拉司群所诱导的生物学变化。
符合条件的未治疗的T1c（≥1.5 cm）-T3、N0、ER阳性/HER2阴性乳腺癌患者，局部评估Ki67≥10%，接受每日剂量345 mg的艾拉司群治疗4周。主要疗效终点是在第28天时完全细胞周期停滞，定义为Ki67≤2.7%。
总体而言，22例患者可评估主要终点。艾拉司群与27.3%的完全细胞周期停滞率相关，且Ki67几何平均变化具有统计学意义，为-52.9%（P = 0.007；95%置信区间，-67.4至-32.1）。值得注意的是，基于PAM50基因特征分析，艾拉司群治疗导致肿瘤表型向更具内分泌敏感性和增殖性更低的方向转变。艾拉司群增加了免疫反应基因（颗粒酶B、CD4和CD抗原8A）的表达，并抑制了增殖和雌激素信号基因（MKI67、雌激素受体1和雄激素受体）。这些生物学变化与第28天时Ki67的抑制水平无关。最常见的不良事件为1级贫血（21.7%）、潮热（8.7%）、便秘（8.7%）和腹痛（8.7%）。1例患者出现3级皮疹，导致治疗中断。未报告其他严重不良事件。
早期乳腺癌患者术前使用艾拉司群治疗显示出相关的生物学和分子反应，并具有可控的安全性。这些发现支持在早期环境中对艾拉司群进行进一步研究。
