Zhang Pin, Sun Tao, Wang Ying, Li Wei, Tong Zhongsheng, Phadke Sneha, Feinstein Trevor, Ma Wenyue, Guo Pengfei, Zhang Minhua, Yue Yong, Xu Binghe
Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Breast Medicine, Liaoning Cancer Hospital, Shenyang, China.
Nat Commun. 2026 Feb 6. doi: 10.1038/s41467-026-69225-2.
This single-arm, phase Ib trial evaluated the antitumor activities and safety of afuresertib (a pan AKT inhibitor) plus fulvestrant for previously treated HR-positive, HER2-negative advanced breast cancer. Eligible patients received afuresertib at 125 mg/day and fulvestrant at 500 mg on days 1, 15, and 29, and every 28 days thereafter during safety run-in and, in the absence of serious toxicities, subsequent 4-week cycles. The trial enrolled 31 patients (median age 54 years; 30 women); 20 received prior CDK4/6 inhibitor therapy. The primary endpoint of investigators-assessed objective response rate was 25.8% (8/31; 90% CI 13.5-41.8). Nine patients (29.0%) had grade 3 or worse adverse events. No death due to adverse event occurred. In conclusion, afuresertib plus fulvestrant was well-tolerated and had promising antitumor activities against pretreated, advanced HR-positive, HER2-negative breast cancer, supporting further studies with randomized controlled trials. This trial is registered with ClinicalTrials.gov (NCT04851613).
这项单臂1b期试验评估了阿福司替尼（一种泛AKT抑制剂）联合氟维司群对既往接受过治疗的激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性晚期乳腺癌的抗肿瘤活性和安全性。符合条件的患者在安全导入期第1、15和29天接受阿福司替尼125毫克/天及氟维司群500毫克治疗，此后每28天一次，若无严重毒性反应，则进入后续的4周周期治疗。该试验纳入了31例患者（中位年龄54岁；30例女性）；20例患者曾接受过细胞周期蛋白依赖性激酶4/6（CDK4/6）抑制剂治疗。研究者评估的主要终点客观缓解率为25.8%（8/31；90%置信区间13.5-41.8）。9例患者（29.0%）发生3级或更严重不良事件。未发生因不良事件导致的死亡。总之，阿福司替尼联合氟维司群耐受性良好，对既往接受过治疗的晚期HR阳性、HER2阴性乳腺癌具有有前景的抗肿瘤活性，支持进一步开展随机对照试验研究。本试验已在ClinicalTrials.gov注册（NCT04851613）。
