富维斯特朗
帕博西利布
医学
内科学
中性粒细胞减少症
肿瘤科
子宫内膜癌
来曲唑
雌激素受体
联合疗法
癌症
抗雌激素
三苯氧胺
不利影响
乳腺癌
转移性乳腺癌
化疗
作者
Angela K. Green,Qin Zhou,Alexia Iasonos,William A. Zammarrelli,Britta Weigelt,Lora H. Ellenson,Rashmi Chhetri-Long,Pooja Shah,Jade Loh,Vania Hom,Pier Selenica,Joseph P. Erinjeri,Iva Petkovska,Sarat Chandarlapaty,Seth Cohen,Rachel N. Grisham,Jason Konner,Maria M. Rubinstein,William P. Tew,Tiffany A. Troso-Sandoval
标识
DOI:10.1158/1078-0432.ccr-24-1999
摘要
Abstract Purpose: Inhibition of the cyclin D–cyclin-dependent kinase (CDK)4/6–INK4–retinoblastoma pathway can overcome acquired or de novo treatment resistance to endocrine monotherapy. Responses to endocrine monotherapy in advanced endometrial cancer are suboptimal, perhaps due to genomic alterations that promote estrogen receptor–independent cyclin D1–CDK4/6 activation. We hypothesized that the addition of abemaciclib, a CDK4/6 kinase inhibitor, to antiestrogen therapy with fulvestrant would be an effective therapeutic strategy in patients with advanced or recurrent endometrial cancer. Patients and Methods: In this phase II study, patients with advanced or recurrent endometrial cancer received 150 mg of abemaciclib orally twice daily with 500 mg of fulvestrant intramuscularly monthly with a 2-week loading dose. Eligibility included estrogen receptor or progesterone receptor expression ≥1% by IHC, measurable disease, ≤2 prior lines of chemotherapy, and ≤1 prior lines of hormonal therapy. The primary endpoint was the objective response rate by RECIST v1.1. Results: Twenty-seven patients initiated therapy, and 25 were evaluable for efficacy. Eleven patients achieved partial response; 10 responses (91%) were in copy number–low/no specific molecular profile tumors, 1 response (9%) was in a microsatellite instability–high tumor, and no responses were observed in copy number–high/TP53abnormal tumors. The objective response rate was 44% (90% confidence interval, 27.0%–62.1%). The median duration of response was 15.6 months. The median progression-free survival was 9.0 months (90% confidence interval, 1.8–20.4). The most common grade ≥3 treatment-related adverse events were neutropenia (26%) and anemia (19%); no new safety signals were identified. Conclusions: The combination of abemaciclib and fulvestrant has promising activity with durable responses in advanced or recurrent endometrial cancer; a randomized trial is planned. See related commentary by Garg and Oza, p. 2073
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