Latest research and application guidelines for second-line treatment of capicitinib combination therapy

Capivasertib, an oral AKT inhibitor, has gained attention in recent years in the second-line treatment of hormone receptor-positive (HR⁺), HER2-negative advanced breast cancer. It is mainly used in patients who have received first-line regimens of endocrine therapy and CDK4/6 inhibitors but have developed resistance or disease progression. The latest clinical research shows that treatment with capositinib combined with fulvestrant can prolong progression-free survival (PFS) and delay chemotherapy, providing patients with a longer non-chemotherapy maintenance period.

In terms of efficacy, the CAPItello‑291 clinical trial showed that the combination regimen significantly delayed disease progression in overall subjects, and was more effective in patients with PI3K/AKT/PTEN pathway abnormalities. The median PFS could reach approximately 7.3 months, which was significantly improved compared to the control group. This therapy is especially suitable for patients who want to delay chemotherapy, reduce the side effects of chemotherapy, and improve their quality of life. It is also suitable for patients with advanced breast cancer whose genetic testing shows pathway abnormalities.

The combination regimen is typically caposetinib plus fulvestrant, sometimes triple therapy in combination with a CDK4/6 inhibitor under experimental conditions. Caposetinib prevents cancer cell proliferation and induces apoptosis by inhibiting the PI3K/AKT signaling pathway. However, this drug is not effective for all patients, and has limited efficacy for patients with normal pathways. At the same time, it is necessary to pay attention to adverse reactions such as blood sugar, blood lipids, liver and kidney function, and skin reactions, and adjust the dose in a timely manner or intermittent administration.
In clinical applications, genetic testing should be conducted under the guidance of doctors to select the most suitable patient group. During treatment, physical indicators need to be monitored regularly, and it is clear that the goal of treatment is to delay disease progression rather than complete cure. In the future, with more real-world studies and the development of new generation AKT/PI3K/mTOR inhibitors, capositinib is expected to play a greater role in second-line and multi-line treatment, providing safer and more effective personalized treatment options for patients with advanced breast cancer.
Reference: https://www.cancer.gov/publications/dictionaries/cancer-drug/def/capivasertib