Does apelvis combined with fulvestrant enter the brain?

Alpelisib (Alpelisib) is a new drug developed for the treatment of patients with estrogen receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer. This drug will be used in combination with Fulvestrant. Fulvestrant is a drug already used to treat advanced breast cancer, and Apelvis targets a very specific enzyme that sends signals to cells to prevent cancer cells from growing and surviving. The combination of oral apelvis and injectable fulvestrant will provide a treatment option for patients with advanced HR+/HER2- breast cancer who have not responded well to other drugs.

Brain metastasis is a common cause of morbidity and death in breast cancer patients. Local central nervous system (CNS)-directed therapy is often the first-line treatment for breast cancer brain metastases (BCBM), but must be followed by systemic therapy to achieve long-term benefit. Among 307 patients with ER+/HER2 metastatic disease, brain metastases were significantly more common in patients with PIK3CA mutations. A retrospective analysis found a significant association between improved survival and continued endocrine therapy after diagnosis of brain metastases. It is worth noting that the clinical benefit rate of the CDK4/6 inhibitor apelvis is 25%.

Preclinical models of breast cancer brain metastasis suggest that PI3K pathway inhibition may be effective in the treatment of brain metastasis. Both SANDPIPER and SOLAR-1 exclude patients with untreated or active CNS metastases; however, buparlisib, the precursor to buparlisib, does have brain penetration, which is thought to be responsible for the higher incidence of mood disorders. The alpha-specific PI3K inhibitor Apelvis significantly did not increase depression, and no significant brain damage was observed in preclinical animal models with an intact blood-brain barrier. Therefore, the activity of apelvis in brain metastases is unknown.