Journal Article

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

Turner, Nicholas C., Jiang, Ou, Wang, Xiaojia, Xiong, Huihua, Lu, Yen-Shen, Teng, Yuee, Li, Wei, Chen, Shin-Cheh, Jiang, Lin, Sun, Tao, Wang, Jingfen, Wu, Xinhong, Fan, Ethan, Yan, Min, Li, Hongsheng, Pang, Danmei, Chen, Wenyan, Zhang, Qingyuan, Tseng, Ling-Ming, Zeng, Xiaoling, Zang, Aimin, Hu, Xichun, Wang, Xian, Collins, Julie M.

2025

Overview

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. The CAPItello-291 phase 3 study reported that capivasertib (an AKT inhibitor) and fulvestrant (a selective estrogen receptor degrader) improved progression free survival in patients with HR-positive/HER2-negative advanced breast cancer. Here, the authors report the results of an extended Chinese cohort recruited as part of the original global CAPItello-291 study.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 38/23 / 59/57 / 59/78 / 631/67/1347 / 631/67/1857 / 692/4028/67/1059 / Adult / Aged / AKT protein / AKT1 protein / Antineoplastic Combined Chemotherapy Protocols - adverse effects / Antineoplastic Combined Chemotherapy Protocols - therapeutic use / Aromatase / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / China / Class I Phosphatidylinositol 3-Kinases - genetics / Class I Phosphatidylinositol 3-Kinases - metabolism / Cohort Studies / Diarrhea / East Asian People / ErbB-2 protein / Estrogen receptors / Estrogens / Female / Fulvestrant / Fulvestrant - administration & dosage / Fulvestrant - adverse effects / Fulvestrant - therapeutic use / Humanities and Social Sciences / Humans / Hyperglycemia / Inhibitors / Middle Aged / multidisciplinary / Next-generation sequencing / Placebos / Progression-Free Survival / Proto-Oncogene Proteins c-akt - genetics / Proto-Oncogene Proteins c-akt - metabolism / PTEN Phosphohydrolase - genetics / PTEN Phosphohydrolase - metabolism / PTEN protein / Pyrimidines - administration & dosage / Pyrimidines - adverse effects / Pyrimidines - therapeutic use / Pyrroles / Receptor, ErbB-2 - genetics / Receptor, ErbB-2 - metabolism / Receptors / Receptors, Estrogen - metabolism / Receptors, Progesterone - metabolism / Science / Science (multidisciplinary) / Survival / Tumors