Capivasertib plus fulvestrant in patients with HR-positive/HER2-negative advanced breast cancer: phase 3 CAPItello-291 study extended Chinese cohort
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 patients with PIK3CA/AKT1/PTEN-non-altered tumors is warranted.
Authors
- Julie Collins (ORCID: https://orcid.org/0000-0001-5702-4693)
- Wenyan Chen (ORCID: https://orcid.org/0000-0001-6730-8702)
- Xiaoling Zeng (ORCID: https://orcid.org/0009-0006-8956-4794)
- Shin‐Cheh Chen (ORCID: https://orcid.org/0000-0002-0177-0045)
- Yen‐Shen Lu (ORCID: https://orcid.org/0000-0001-7461-1291)
- Ou Jiang (ORCID: https://orcid.org/0000-0002-3455-9676)
- Jingfen Wang
- Ling‐Ming Tseng (ORCID: https://orcid.org/0000-0002-4648-6646)
- Min Yan (ORCID: https://orcid.org/0000-0002-3911-748X)
- Nicholas C. Turner (ORCID: https://orcid.org/0000-0001-8937-0873)
- Tao Sun (ORCID: https://orcid.org/0000-0001-5931-386X)
- Xichun Hu (ORCID: https://orcid.org/0000-0001-6148-9186)
- Aimin Zang (ORCID: https://orcid.org/0000-0003-1681-831X)
- Wei Li (ORCID: https://orcid.org/0000-0002-3332-1287)
- Xian Wang (ORCID: https://orcid.org/0000-0003-0041-7589)
- Jiang Lin (ORCID: https://orcid.org/0000-0002-4704-9157)
- Xiaojia Wang (ORCID: https://orcid.org/0000-0002-7005-0842)
- Hongsheng Li (ORCID: https://orcid.org/0000-0002-2664-7975)
- Qingyuan Zhang (ORCID: https://orcid.org/0000-0001-8116-5293)
- Xinhong Wu
- Danmei Pang (ORCID: https://orcid.org/0009-0001-6802-029X)
- Yuee Teng (ORCID: https://orcid.org/0009-0000-3759-6707)
- Huihua Xiong
- E. Fan
Institutions
- Institute of Cancer Research (GB)
- Harbin Medical University (CN)
- Jilin University (CN)
- Sir Run Run Shaw Hospital (CN)
- Taipei Veterans General Hospital (TW)
- Chang Gung Memorial Hospital (TW)
- Zhengzhou University (CN)
- Fudan University Shanghai Cancer Center (CN)
- Linyi People's Hospital (CN)
- Zhejiang Cancer Hospital (CN)
- Third Affiliated Hospital of Harbin Medical University (CN)
- First People's Hospital of Foshan (CN)
- Third Hospital of Nanchang (CN)
- Linkou Chang Gung Memorial Hospital (TW)
- Neijiang Normal University (CN)
- Royal Marsden Hospital (GB)
- First Hospital of Jilin University (CN)
- National Taiwan University Hospital (TW)
- First Hospital of China Medical University (CN)
- Affiliated Hospital of Hebei University (CN)
- Xian Yang Central Hospital (CN)
- AstraZeneca (United States) (US)
- Guangzhou Medical University Cancer Hospital (CN)
- Tongji Hospital (CN)
- Hubei Cancer Hospital (CN)
- Liaoning Cancer Hospital & Institute (CN)
- Huazhong University of Science and Technology (CN)
- Zhejiang University (CN)
- China Medical University (CN)
- Guangzhou Medical University (CN)
Publication Details
- Journal
- Nature Communications
- Published
- 2025-05-09
- DOI
- https://doi.org/10.1038/s41467-025-59210-6
- Citations
- 9
- Primary Topic
- Advanced Breast Cancer Therapies
- Type
- article
- Field-Weighted Citation Impact
- 13.67
Funders
- AstraZeneca
- Astex Pharmaceuticals