Capivasertib联合阿比特龙治疗PTEN缺失的初诊转移性激素敏感性前列腺癌：CAPItello-281试验的更新生存分析。
完整摘要 · 中文译文
背景：携带磷酸酶与张力蛋白同源基因（PTEN）缺失的初治转移性激素敏感性前列腺癌（mHSPC）患者预后较差，且从当前标准治疗中获益减少。III期CAPItello-281研究（NCT04493853）显示，capivasertib联合阿比特龙对比安慰剂联合阿比特龙（联合泼尼松/泼尼松龙及雄激素剥夺治疗）在影像学无进展生存期（rPFS）方面具有统计学显著获益：风险比（HR）0.81，95%置信区间（CI）0.66-0.98；P=0.034。期中总生存期（OS；数据成熟度26%）的HR为0.90，95% CI 0.71-1.15。本文报告在OS数据成熟度42%时的临时、描述性分析。 患者与方法：初治mHSPC且PTEN缺失肿瘤（定义为免疫组织化学染色显示≥90%的存活恶性细胞无特异性胞质染色）的患者，接受capivasertib联合阿比特龙或匹配安慰剂（按1:1随机化）联合阿比特龙治疗。在本次临时数据截止时进行的分析，包括受α控制的OS关键次要终点以及研究者评估的rPFS主要终点，均为描述性分析，并非方案预设。 结果：1012例患者接受capivasertib联合阿比特龙（n=507）或安慰剂联合阿比特龙（n=505）。在OS成熟度42%的本次临时分析中（数据截止日期：2026年3月9日），额外随访17个月（两臂中位随访均为39个月），OS的HR支持capivasertib联合阿比特龙优于安慰剂联合阿比特龙（HR 0.82，95% CI 0.68-0.99，P=0.044），且OS中位…… edians 达到：57.4 对 46.5 个月。更新后的影像学无进展生存期（rPFS）（HR 0.83，95% CI 0.70-0.99，名义 P=0.033；中位数 35.5 对 26.0 个月）与主要分析一致。安全性特征与主要发现保持一致。结论：随着随访时间延长，这项更新描述性分析的结果支持在 PTEN 缺陷型转移性激素敏感性前列腺癌（mHSPC）患者治疗中，在阿比特龙基础上加用卡匹色替具有临床意义的总生存期（OS）获益。卡匹色替联合阿比特龙代表了针对这一预后不良且高度未满足需求人群的同类首个靶向治疗方法。
完整摘要 · 英文原文
BACKGROUND: Patients with phosphatase and tensin homolog (PTEN)-deficient de novo metastatic hormone-sensitive prostate cancer (mHSPC) have poor prognosis and reduced benefit from current standard of care. The phase III CAPItello-281 study (NCT04493853) showed a statistically significant benefit in radiographic progression-free survival (rPFS) with capivasertib plus abiraterone versus placebo plus abiraterone (combined with prednisone/prednisolone and androgen deprivation therapy): hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.66-0.98; P=0.034. The HR for interim overall survival (OS; 26% maturity) was 0.90, 95% CI 0.71-1.15. Here, we report ad hoc, descriptive analyses at 42% OS data maturity. PATIENTS AND METHODS: Patients with de novo mHSPC and PTEN-deficient tumors (defined as ≥90% of viable malignant cells with no specific cytoplasmic staining by immunohistochemistry) received capivasertib plus abiraterone or matched placebo (randomized 1:1) plus abiraterone. Analyses performed at this ad hoc data cut-off, including the alpha-controlled key secondary endpoint of OS as well as the primary endpoint of investigator-assessed rPFS, were descriptive and not prespecified in the protocol. RESULTS: 1012 patients received capivasertib plus abiraterone (n=507) or placebo plus abiraterone (n=505). At this ad hoc analysis at 42% OS maturity (data cut-off: March 9, 2026), with 17 months' additional follow-up (median follow-up 39 months in both arms), HR for OS favored capivasertib plus abiraterone versus placebo plus abiraterone (HR 0.82, 95% CI 0.68-0.99, P=0.044) and OS medians were reached: 57.4 versus 46.5 months. Updated rPFS (HR 0.83, 95% CI 0.70-0.99, nominal P=0.033; median 35.5 versus 26.0 months) was consistent with the primary analysis. The safety profile remained consistent with the primary findings. CONCLUSIONS: With longer follow-up, findings from this updated descriptive analysis support the clinically meaningful OS benefit of adding capivasertib to abiraterone in the treatment of patients with PTEN-deficient mHSPC. Capivasertib plus abiraterone represents a first-in-class targeted treatment approach for this poor prognosis population with high unmet need.