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Dalpiciclib in combination with letrozole/anastrozole or fulvestrant in HR-positive and HER2-negative advanced breast cancer: results from a phase Ib study.
Zhang, Qingyuan; Zhang, Pin; Yan, Min; Yan, Xi; Wang, Xian; Gu, Yuanting; Qu, Xiujuan; Li, Shaorong; Xu, Guoying; Zhu, Xiaoyu; Xu, Binghe.
Afiliación
  • Zhang Q; Department of Medical Oncology, Harbin Medical University Cancer Hospital, Harbin, China.
  • Zhang P; National Cancer Center and Clinical Trial Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
  • Yan M; Department of Breast Disease, Henan Breast Cancer Center, The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China.
  • Yan X; Department of Head and Neck Cancer, West China Hospital, Sichuan University, Chengdu, China.
  • Wang X; Department of Medical Oncology, Sir Run Run Shaw Hospital, Hangzhou, China.
  • Gu Y; Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
  • Qu X; Department of Medical Oncology, The First Affiliated Hospital of China Medical University, Shenyang, China.
  • Li S; Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
  • Xu G; Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
  • Zhu X; Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
  • Xu B; National Cancer Center and Clinical Trial Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 17 Panjiayuan South Lane, Chaoyang District, Beijing 100021, China.
Ther Adv Med Oncol ; 16: 17588359241273026, 2024.
Article en En | MEDLINE | ID: mdl-39229468
ABSTRACT

Background:

Dalpiciclib is a novel cyclin-dependent kinase 4/6 inhibitor which showed tolerability and preliminary efficacy as monotherapy for pretreated advanced breast cancer (BC).

Objectives:

To further assess dalpiciclib with endocrine therapy (ET) in hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative BC.

Design:

A multicenter, open-label, phase Ib trial.

Methods:

Patients with locally recurrent or metastatic BC were enrolled in five cohorts. Patients without prior treatment for advanced disease (cohorts 1-2) were given dalpiciclib (125 or 150 mg) plus letrozole/anastrozole; patients who progressed after ET (cohorts 3-5) were given dalpiciclib (125, 150, or 175 mg) plus fulvestrant. Dalpiciclib was administered orally once daily in 3-weeks-on/1-week off schedule. The primary endpoint was safety.

Results:

A total of 58 patients received dalpiciclib with letrozole/anastrozole and 46 received dalpiciclib with fulvestrant. No maximum tolerated dose of dalpiciclib was reached with letrozole/anastrozole or fulvestrant. Across all cohorts, 86.7%-93.8% of patients had a grade ⩾3 adverse event, with the most common being neutropenia (grade 3, 40.0% for dalpiciclib 175 mg and 61.8%-87.5% for lower doses; grade 4, 46.7% and 4.2%-20.6%, respectively) and leukopenia (grade 3, 80.0% for 175 mg and 33.3%-54.2% for lower doses; grade 4, 0% for all doses). At tested dose levels, steady-state areas under the concentration curve and peak concentration of dalpiciclib increased with dose when combined with letrozole/anastrozole and fulvestrant. Dalpiciclib at 150 mg was associated with a numerically higher objective response rate in both patients untreated for advanced disease (67.6%; 95% confidence interval (CI) 49.5-82.6) and patients progressing after ET (53.3%; 95% CI 26.6-78.7); as of July 30, 2022, the median progression-free survival with dalpiciclib 150 mg was 24.1 months (95% CI 16.9-46.0) with letrozole/anastrozole and 16.7 months (95% CI 1.9-24.1) with fulvestrant.

Conclusion:

Dalpiciclib plus letrozole/anastrozole or fulvestrant showed an acceptable safety profile. The recommended phase III dose of dalpiciclib was 150 mg. Trial registration ClinicalTrials.gov identifier NCT03481998.
Palabras clave

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Ther Adv Med Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Ther Adv Med Oncol Año: 2024 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido