Capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer: phase 3 CAPItello-291 study extended Chinese cohort

作者：Xichun Hu, Qingyuan Zhang, Tao Sun, Huihua Xiong, Wei Li, Yuee Teng, Yen‐Shen Lu, Ling‐Ming Tseng, Min Yan, Hongsheng Li, Danmei Pang, Shin‐Cheh Chen, Wenyan Chen, Ou Jiang, Jingfen Wang, Xinhong Wu, Xian Wang, Aimin Zang, Xiaojia Wang, Julie Collins, Ethan Fan, Lin Jiang, Xiaoling Zeng, Nicholas C. Turner · 发表于：Nature Communications · 年份：2025 · DOI：10.1038/s41467-025-59210-6 · 被引用次数：16 · 研究领域：Advanced Breast Cancer Therapies、HER2/EGFR in Cancer Research、PI3K/AKT/mTOR signaling in cancer

In the global CAPItello-291 randomized phase 3 study (NCT04305496) in patients with hormone receptor-positive/HER2-negative advanced breast cancer and progression during/after aromatase inhibitor treatment, capivasertib-fulvestrant significantly improved progression-free survival (PFS) in the overall population and patients with PIK3CA/AKT1/PTEN-altered tumors versus placebo-fulvestrant. We assessed efficacy and safety of capivasertib-fulvestrant in a prespecified exploratory analysis of a Chinese cohort (n = 24) and extended study with the same protocol (n = 110). Clinically meaningful PFS benefit for capivasertib-fulvestrant was observed in the overall population (median PFS: 6.9 [capivasertib-fulvestrant] versus 2.8 [placebo-fulvestrant] months; hazard ratio 0.51, 95% CI 0.34-0.76), patients with PIK3CA/AKT1/PTEN-altered tumors (n = 46; 5.7 versus 1.9 months; hazard ratio 0.41, 95% CI 0.19-0.85) and PIK3CA/AKT1/PTEN-non-altered tumors (patients with confirmed next-generation sequencing results [n = 68]; 9.2 versus 2.7 months; hazard ratio 0.38; 95% CI 0.21-0.68). The most frequent adverse events (AEs) with capivasertib-fulvestrant were diarrhea (60.6% versus 11.3% with placebo-fulvestrant) and hyperglycemia (57.7% versus 17.7%). AEs leading to capivasertib-fulvestrant discontinuation were reported in 11.3% of patients versus 3.2% for placebo-fulvestrant. The benefit-risk profile of capivasertib-fulvestrant in the Chinese cohort was favorable; further exploration in patient...