Aboud Karam, Meissner Magda, Jones Rob
Velindre Cancer Centre, Cardiff University School of Medicine, DCG, Velindre Road, Cardiff CF14 2TL, UK.
Velindre Cancer Centre, Cardiff University School of Medicine, DCG, Cardiff, UK.
Ther Adv Med Oncol. 2025 Jul 31;17:17588359251358947. doi: 10.1177/17588359251358947. eCollection 2025.
The landscape of breast cancer treatment continues to evolve. Survival rates have improved due to advancements in treatments such as endocrine therapy, cyclin-dependent kinase 4/6 inhibitors and targeted therapies. The PI3K/AKT/PTEN signalling pathway, frequently mutated in breast cancer, is a key target. Capivasertib, an AKT inhibitor, has shown promise in pre-clinical studies and clinical trials as monotherapy and in combination with Fulvestrant. The FAKTION trial demonstrated the efficacy and safety of Capivasertib with Fulvestrant, particularly in patients with PI3K/AKT/PTEN alterations. The Capitello 291 trial further supported the observed efficacy of Capivasertib with Fulvestrant in the FAKTION trial. Notably, Capivasertib plus Fulvestrant received Food and Drug Administration (FDA) approval in 2023 for ER-positive/HER2-negative breast cancer with PI3K/AKT/PTEN alterations. More recently, the National Institute for Health and Care Excellence (NICE) has also given approval for Capivasertib and Fulvestrant in this setting in May 2025. Moreover, evidence suggests further potential useful combinations of Capivasertib in other breast cancer settings, including triple-negative breast cancer. In conclusion, the evolving understanding of molecular pathways in breast cancer, coupled with successful clinical trials and regulatory approvals, positions Capivasertib plus Fulvestrant as a promising addition to standard care for ER-positive/HER2-negative breast cancer. Further research is required to compare the efficacy of available agents, explore the optimal sequence of treatment and establish the best drug combinations for ER-positive/HER2-negative breast cancer patients.
乳腺癌治疗格局不断演变。由于内分泌治疗、细胞周期蛋白依赖性激酶4/6抑制剂和靶向治疗等治疗方法的进步，生存率有所提高。PI3K/AKT/PTEN信号通路在乳腺癌中经常发生突变，是一个关键靶点。AKT抑制剂卡匹西利在临床前研究和临床试验中作为单一疗法以及与氟维司群联合使用均显示出前景。FAKTION试验证明了卡匹西利与氟维司群联合使用的疗效和安全性，特别是在PI3K/AKT/PTEN改变的患者中。Capitello 291试验进一步支持了FAKTION试验中观察到的卡匹西利与氟维司群联合使用的疗效。值得注意的是，卡匹西利加氟维司群于2023年获得美国食品药品监督管理局（FDA）批准，用于治疗伴有PI3K/AKT/PTEN改变的雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌。最近，英国国家卫生与临床优化研究所（NICE）也于2025年5月批准了卡匹西利和氟维司群用于这种情况。此外，有证据表明卡匹西利在其他乳腺癌环境中，包括三阴性乳腺癌中，还有进一步潜在的有用联合方案。总之，对乳腺癌分子通路不断深入的了解，加上成功的临床试验和监管批准，使卡匹西利加氟维司群有望成为雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌标准治疗的补充。需要进一步研究来比较现有药物的疗效，探索最佳治疗顺序，并为雌激素受体阳性/人表皮生长因子受体2阴性乳腺癌患者确定最佳药物组合。
