Capivasertib/Fulvestrant in patients with HR+, HER2-low or HER2-negative locally advanced or metastatic breast cancer.

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.