■雌激素受体阳性(ER),具有ESR1突变的人表皮生长因子受体2阴性(HER2-)乳腺癌由于其对化疗的适应性耐药机制而提出了重大的治疗挑战。尤其是内分泌治疗。Elacestrant,一种新型口服选择性雌激素受体降解剂(SERD),在这个抗治疗的时代已经成为一种有前途的药物。
■对关键的临床试验进行了全面的搜索,包括RAD1901-005试验,翡翠审判,ELIPSE,和电梯,专注于他们的方法论,患者群体,治疗方案,和结果。
■这篇叙述性综述描述了关于elacestrant的临床前和临床证据,专注于它的药效学,药代动力学,功效,和现有文献中的安全性。Elacestrant已证明对与对一线内分泌疗法的抗性相关的ESR1突变具有出色的活性。临床试验显示,晚期ER+/HER2-患者的无进展生存期改善,ESR1突变乳腺癌。安全性特征表明与其他药剂一致的可耐受的副作用谱。它的口服生物利用度提供了一个方便的替代注射SERD,对患者依从性和生活质量有潜在影响。该综述还讨论了elacstrant相对于现有内分泌疗法的比较疗效及其在联合治疗方案中的可能用途。
■正在进行的评估elacestrant和其他SERD的临床试验将产生可能有助于临床医生确定ER+乳腺癌内分泌治疗药物的最佳选择和顺序的数据。靶向和免疫治疗剂与传统化疗的整合代表了乳腺癌治疗的关键转变。朝着更加个性化和有效的方案迈进。
UNASSIGNED: Estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) breast cancer with ESR1 mutations presents a significant therapeutic challenge due to its adaptive resistance mechanisms to chemotherapy, especially endocrine treatment. Elacestrant, a novel oral selective estrogen receptor degrader (SERD), has emerged as a promising agent in this treatment-resistant era.
UNASSIGNED: A comprehensive search was conducted on pivotal clinical trials, including the RAD1901-005 Trial, EMERALD TRIAL, ELIPSE, and ELEVATE, focusing on their methodologies, patient populations, treatment regimens, and outcomes.
UNASSIGNED: This narrative review describes the available preclinical and clinical evidence on elacestrant, focusing on its pharmacodynamics, pharmacokinetics, efficacy, and safety within the existing literature. Elacestrant has demonstrated excellent activity against ESR1 mutations associated with resistance to first-line endocrine therapies. Clinical trials have shown improved progression-free survival in patients with advanced ER+/HER2-, ESR1-mutated breast cancer. Safety profiles indicate a tolerable side effect spectrum consistent with other agents. Its oral bioavailability offers a convenient alternative to injectable SERDs, with potential implications for patient adherence and quality of life. The review also discusses the comparative efficacy of elacestrant relative to existing endocrine therapies and its possible use in combination regimens.
UNASSIGNED: Ongoing clinical trials assessing elacestrant and other SERDs will yield data that might aid clinicians in determining the optimal selection and order of endocrine treatment drugs for ER+ breast cancer. The integration of targeted and immunotherapeutic agents with traditional chemotherapy represents a pivotal shift in Breast Cancer treatment, moving towards more personalized and effective regimens.