Hu Xichun, Zhang Qingyuan, Sun Tao, Xiong Huihua, Li Wei, Teng Yuee, Lu Yen-Shen, Tseng Ling-Ming, Yan Min, Li Hongsheng, Pang Danmei, -Chen Shin-Cheh, Chen Wenyan, Jiang Ou, Wang Jingfen, Wu Xinhong, Wang Xian, Zang Aimin, Wang Xiaojia, Collins Julie M, Fan Ethan, Jiang Lin, Zeng Xiaoling, Turner Nicholas C
Department of Medical Oncology, Fudan University Shanghai Cancer Center; Fudan University, Shanghai, China.
Harbin Medical University Cancer Hospital, Harbin, China.
Nat Commun. 2025 May 9;16(1):4324. doi: 10.1038/s41467-025-59210-6.
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.
在一项针对激素受体阳性/人表皮生长因子受体2阴性晚期乳腺癌且在芳香化酶抑制剂治疗期间/之后病情进展的患者的全球CAPItello-291随机3期研究（NCT04305496）中，与安慰剂-氟维司群相比，卡哌西利-氟维司群显著改善了总体人群以及携带PIK3CA/AKT1/PTEN改变肿瘤患者的无进展生存期（PFS）。我们在一个中国队列（n = 24）的预先指定探索性分析以及采用相同方案的扩展研究（n = 110）中评估了卡哌西利-氟维司群的疗效和安全性。在总体人群中观察到卡哌西利-氟维司群具有临床意义的PFS获益（中位PFS：卡哌西利-氟维司群为6.9个月，安慰剂-氟维司群为2.8个月；风险比0.51，95%置信区间0.34 - 0.76），在携带PIK3CA/AKT1/PTEN改变肿瘤的患者中（n = 46；5.7个月对1.9个月；风险比0.41，95%置信区间0.19 - 0.85）以及携带PIK3CA/AKT1/PTEN未改变肿瘤的患者中（经确认的下一代测序结果的患者[n = 68]；9.2个月对2.7个月；风险比0.38；95%置信区间0.21 - 0.68）。卡哌西利-氟维司群最常见的不良事件（AE）是腹泻（60.6%对安慰剂-氟维司群的11.3%）和高血糖（57.7%对17.7%）。因AE导致卡哌西利-氟维司群停药的患者报告率为11.3%，而安慰剂-氟维司群为3.2%。卡哌西利-氟维司群在中国队列中的获益-风险特征良好；有必要对携带PIK3CA/AKT1/PTEN未改变肿瘤的患者进行进一步探索。
