1. Proxalutamide in patients with AR-positive metastatic breast cancer: Results from an open-label multicentre phase Ib study and biomarker analysis
- Author
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Hanfang Jiang, Quchang Ouyang, Yongmei Yin, Zhongshen Tong, Kunwei Shen, Zhongyu Yuan, Cuizhi Geng, Yaxin Liu, Guohong Song, Ran Ran, Wei Li, Qing Qu, Meiyu Wang, Luping Meng, Youzhi Tong, and Huiping Li
- Subjects
Cancer Research ,Treatment Outcome ,Oncology ,Antineoplastic Combined Chemotherapy Protocols ,Androgen Receptor Antagonists ,Humans ,Female ,Breast Neoplasms ,Biomarkers - Abstract
Proxalutamide is a novel second-generation non-steroidal androgen receptor (AR) antagonist. This study aimed to evaluate the preliminary efficacy and safety of proxalutamide in patients with AR-positive metastatic breast cancer (ARIn this open-label, dose-expansion, multicentre phase Ib trial, patients with ARForty-five patients with three median lines (range, 1-13) prior systemic therapy were enrolled (cohort A, n = 30; cohort B, n = 15). Among 39 evaluable patients, DCR at 8 and 16 weeks was 25.6% (95% confidence interval [CI], 11.9-39.4%), with 26.9% in cohort A and 23.1% in cohort B. No patient achieved partial response or complete response. Proxalutamide 200 mg/day was determined as RP2D. The 6-month progression-free survival (PFS) rate was 19.6% (95% CI, 10.2-37.5%). In the triple-negative subgroup, DCR at 8 weeks was 38.5%, with median PFS of 9.1 months (95% CI, 7.8-NA) in those who achieved response at 8 weeks (n = 5). Most common grade 3/4 adverse events were aspartate aminotransferase increase (8.9%) and γ-glutamyltransferase increase (8.9%). By biomarker analysis, patients with moderate AR expression of IHC (26%-75%), PIK3CA pathogenic mutations, or60 ng/ml cell-free DNA yield showed longer PFS.Proxalutamide showed promising anti-tumour activity with good tolerability in patients with heavily pretreated ARThis clinical study was prospectively registered at chinadrugtrials.org.cn (Identifier: CTR20170757) and clinical trials.gov (Identifier: NCT04103853).
- Published
- 2022