维普德格斯特兰特是一种PROTAC雌激素受体降解剂,用于晚期乳腺癌患者
Mario Campone1, Michelino De Laurentiis2, Komal Jhaveri3,4
1Institut de Cancérologie de l'Ouest Angers-Nantes, Saint-Herblain, France.
The New England journal of medicine
|June 2, 2025
概括
在患有ESR1突变的晚期乳腺癌患者中,Vepdegestrant的无进展生存时间比fulvestrant更长. 然而,在整体患者群体中没有观察到这种益处.
科学领域:
- 在瘤学瘤学.
- 药理学 药理学是指药理学的学科.
- 遗传学 遗传学 是一个
背景情况:
- 维普德格斯特兰特是一种口服蛋白质分解向化母体 (PROTAC) 雌激素受体 (ER) 降解剂.
- 它直接利用无素-蛋白酶体系统进行向的蛋白质降解.
研究的目的:
- 在ER阳性,HER2阴性晚期乳腺癌患者中,与富尔韦斯特兰特相比,评估韦普德格斯特兰特的疗效.
- 评估ESR1突变和没有ESR1突变的患者的无进展生存期 (PFS).
主要方法:
- 第三阶段,开放标签,随机试验比较vepdegestrant (每天200毫克) 和fulvestrant (500毫克).
- 这些患者之前接受过CDK4/6抑制剂和内分泌疗法.
- 随机化被根据ESR1突变状态和内脏疾病的存在分层.
主要成果:
- 在270名ESR1突变患者中,PFS的中位数为vepdegestrant的5.0个月,而fulvestrant的2.1个月 (HR,0.58;P<0.001).
- 在整体人群中 (624名患者),PFS的中位数为3.8个月的vepdegestrant与3.6个月的fulvestrant (HR,0.83;P=0.07).
- 3级以上的不良事件发生在23.4%的vepdegestrant患者和17.6%的fullvestrant患者中.
结论:
- 在ESR1突变的晚期乳腺癌患者中,Vepdegestrant的PFS明显长于fulvestrant.
- 在整体患者群体中,没有观察到德格斯特兰特对PFS的显著益处.
- 该研究强调ESR1突变状态在指导晚期乳腺癌治疗决策中的重要性.
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