美国食品和药物管理局 (FDA) 批准 capivasertib 与氟维司群联合用于治疗激素受体阳性、人表皮生长因子受体 2 (HER2) 阴性、局部晚期或转移性乳腺癌 (MBC) 成年患者，这些患者曾接受过既往至少接受过一次内分泌治疗，且其肿瘤存在一种或多种磷脂酰肌醇 3 激酶 (PIK3CA)/AKT 丝氨酸/苏氨酸激酶 1 (AKT1)/磷酸酶和张力蛋白同源物 (PTEN) 改变，经 FDA 批准的测试检测到。基于 CAPtello-291，这是一项随机、双盲、多中心试验，纳入了 708 名激素受体阳性、HER2 阴性晚期或 MBC 患者，其中包括 289 名 PIK3CA/AKT1/PTEN 肿瘤改变患者。患者以 1:1 的比例随机分配，接受 capivasertib 400 mg 每日两次、每周 4 天的氟维司群治疗组与安慰剂组的氟维司群治疗组。随机分配根据是否存在肝转移、既往接受过 CDK4/6i、细胞周期蛋白依赖性激酶四和六 (CDK4/6) 抑制剂以及地理区域进行分层。总体人群（风险比 [HR]，0.6 [95% CI，0.51 至 0.71]）；这一结果是由生物标志物阳性人群中的 289 名患者得出的（HR，0.5 [95% CI，0.37 至 0.68]）。对生物标志物阴性人群中 313 名 (44%) 患者的研究者评估 PFS 进行的探索性分析显示，获益不确定（HR，0.78 [95% CI，0.60 至 1.01]）。使用 capivasertib 时，更多患者出现 ≥3 级毒性。主要问题包括高血糖（18% 所有级别，2.8% ≥3 级）、皮肤毒性（58% 所有级别，17% ≥3 级）和腹泻（72% 所有级别，9% ≥3 级）。 Capivasertib 联合氟维司群被批准用于肿瘤存在 PIK3CA/AKT1/PTEN 改变的患者。该亚组的获益-风险评估是有利的，因为在可接受的安全性背景下，PFS 具有统计学意义和临床意义的改善，包括没有证据表明对总生存期有潜在损害。相比之下，生物标志物阴性人群的获益-风险是不利的。

The US Food and Drug Administration (FDA) approved capivasertib in combination with fulvestrant for adult patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative, locally advanced, or metastatic breast cancer (MBC) who have received at least one previous endocrine therapy and whose tumors harbor one or more phosphatidylinositol 3-kinase (PIK3CA)/AKT Serine/Threonine Kinase 1 (AKT1)/phosphatase and tensin homolog (PTEN) alterations, as detected by an FDA-approved test.Approval was based on CAPItello-291, a randomized, double-blind, multicenter trial of 708 patients with hormone receptor-positive, HER2-negative advanced or MBC, including 289 patients with PIK3CA/AKT1/PTEN tumor alterations. Patients were randomly assigned 1:1 to receive capivasertib 400 mg twice daily for 4 days per week with fulvestrant versus placebo with fulvestrant. Random assignment was stratified by presence of liver metastases, previous treatment with CDK4/6i, cyclin-dependent kinase four and six (CDK4/6) inhibitors, and geographical region.A statistically significant progression-free survival (PFS) benefit was demonstrated in the overall population (hazard ratio [HR], 0.6 [95% CI, 0.51 to 0.71]); this result was driven by 289 patients in the biomarker-positive population (HR, 0.5 [95% CI, 0.37 to 0.68]). An exploratory analysis of investigator-assessed PFS in the 313 (44%) patients in the biomarker-negative population showed uncertain benefit (HR, 0.78 [95% CI, 0.60 to 1.01]). With capivasertib, more patients had Grade ≥3 toxicities. Key concerns included hyperglycemia (18% all-grade, 2.8% Grade ≥3), cutaneous toxicity (58% all-grade, 17% Grade ≥3), and diarrhea (72% all-grade, 9% Grade ≥3).Capivasertib with fulvestrant was approved for patients whose tumors harbored PIK3CA/AKT1/PTEN alterations. Benefit-risk assessment in this subgroup was favorable based on a statistically significant and clinically meaningful improvement in PFS in the context of an acceptable safety profile including no evidence of a potential detriment in overall survival. By contrast, the benefit-risk was unfavorable in the biomarker-negative population.