Capivasertib plus abiraterone in PTEN-deficient metastatic hormone-sensitive prostate cancer: CAPItello-281 phase III study.

Dual inhibition of PI3K/AKT and AR pathways with capivasertib and abiraterone may delay progression and improve disease outcomes.

使用卡比塞特和阿比特龙双重抑制PI3K/AKT和AR通路可能会延迟疾病进展并改善疾病结果。

patients_and_methods

In CAPItello-281 (NCT04493853), patients with PTEN-deficient mHSPC (diagnostic cut-off: ≥90% viable malignant cells with no specific cytoplasmic PTEN immunohistochemistry staining) received capivasertib or placebo (1 : 1) plus abiraterone, prednisone/prednisolone, and androgen deprivation therapy (ADT).

在CAPItello-281 (NCT04493853)试验中，具有PTEN缺陷的转移性激素敏感性前列腺癌（mHSPC）患者（诊断标准：≥90%的可存活恶性细胞无特定的细胞质PTEN免疫组化染色缺失）接受了卡比司他或安慰剂（1:1）联合阿比特龙、泼尼松/泼尼松龙和雄激素剥夺治疗（ADT）。

The primary endpoint was investigator-assessed radiographic progression-free survival(rPFS); overall survival(OS) was a key secondary endpoint.

主要终点是研究者评估的影像学无进展生存期（rPFS）；总生存期（OS）是一个关键的次要终点。

Post hoc exploratory subgroups at increasing PTEN cut-off thresholds were also assessed.

还评估了在增加PTEN阈值切点的后续探索性亚组。

Results

25.3% (1519/6003) of patients with valid tumor test results had PTEN-deficient tumors.

在有有效肿瘤检测结果的患者中，25.3%（1519/6003）的患者存在PTEN缺陷肿瘤。

In the randomized PTEN-deficient population, a statistically significant improvement in rPFS was observed with capivasertib plus abiraterone (n = 507, median 33.2 months) versus placebo plus abiraterone [n = 505, 25.7 months; hazard ratio(HR) 0.81, 95% confidence interval(CI) 0.66-0.98, P = 0.034].

在随机化的PTEN缺陷人群中，观察到卡比瓦塞特加阿比特龙组（n = 507，中位无进展生存期为33.2个月）与安慰剂加阿比特龙组（n = 505，25.7个月；风险比（HR）0.81，95%置信区间（CI）0.66-0.98，P = 0.034）相比，无进展生存期（rPFS）有统计学显著性改善。

Post hoc rPFS analyses for loss of PTEN cut-offs of ≥95%, ≥99%, and 100% showed that the capivasertib plus abiraterone arm performed consistently across cut-offs, but the placebo plus abiraterone arm performed progressively worse as the cut-off for the degree of PTEN loss was increased, resulting in a numerically improved treatment effect.

事后分析rPFS，对于PTEN丧失度≥95%，≥99%和100%的截断值显示，卡比瓦塞特加阿比特龙组在各个截断值上表现一致，但安慰剂加阿比特龙组随着PTEN丧失度截断值的增加，表现逐渐变差，导致治疗效果数值上有所改善。

In the overall population studied, the HR for OS (26.4% maturity) was 0.90, 95% CI 0.71-1.15, P = 0.401.

在研究的总体人群中，总生存（OS）的风险比（HR）（成熟度为26.4%）为0.90，95%置信区间（CI）为0.71-1.15，P值为0.401。

The most common adverse events (AEs) for capivasertib plus abiraterone were diarrhea (51.9%; 8.0% placebo plus abiraterone), hyperglycemia (38.0%; 12.9%), and rash (35.4%; 7.0%).

卡比沙替布联合阿比特龙最常见的不良事件（AEs）为腹泻（51.9%；安慰剂加阿比特龙为8.0%），高血糖（38.0%；12.9%），以及皮疹（35.4%；7.0%）。

Deaths associated with an AE were reported in 36 (7.2%) and 26 (5.2%) patients in the capivasertib plus abiraterone and placebo plus abiraterone arms, respectively.

在卡比沙替尼联合阿比特龙组和安慰剂联合阿比特龙组中，分别有36名（7.2%）和26名（5.2%）患者报告了与不良事件相关的死亡。

Conclusions

Capivasertib plus abiraterone improves rPFS versus placebo plus abiraterone in PTEN-deficient mHSPC, on a background of ADT, with a 7.5-month improvement in median rPFS.

卡比沙替尼联合阿比特龙在雄激素剥夺治疗（ADT）背景下，对于PTEN缺陷型转移性激素敏感性前列腺癌（mHSPC）患者，与安慰剂联合阿比特龙相比，中位无进展生存期（rPFS）提高了7.5个月。

AE profile was consistent with that of the individual agents.

不良事件（AE）特征与单独使用各药物时一致。

Patients with PTEN-deficient mHSPC benefit from dual blockade of the PI3K/AKT and AR pathways with capivasertib plus abiraterone.

PTEN缺陷型转移性激素敏感性前列腺癌（mHSPC）患者从使用卡皮瓦塞替布联合阿比特龙进行PI3K/AKT和雄激素受体（AR）通路的双重阻断中获益。