Trial of Apelvis to Treat Excessive Blood Vessel Growth

PIK3CA-related overgrowth spectrum (PROS) is a disorder caused by somatic recessive gain-of-function mutations in the gene encoding phosphatidylinositol-3-kinase (PI3K). PROS is rare and affects many different tissues, including skin, bone, blood vessels, fat, and connective tissue, so its manifestations vary widely. The disease usually does not affect all cells in the body. In patients with PROS, there is a gain-of-function mutation in the PI3K α catalytic subunit PIK3CA. This mutation causes bone and soft tissue deformities and tumor formation.

For patients 2 years of age and older who require systemic therapy, Alpelisib is an option that recently received accelerated approval from the U.S. Food and Drug Administration (FDA) on April 5, 2022, in a once-daily oral formulation to reduce and prevent lesions. Prior to its approval for the treatment of PROS, Apelvis, branded as Piqray, was indicated for postmenopausal women and men with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer.

The FDA's approval of apelvis for use in adult and pediatric patients older than 2 years with PROS is based on an observational, retrospective chart review of patients who received apelvis through the Compassionate Use Stewardship Access Program. This study is also known as the EPIK-P1 study. A detailed report on the EPIK-P1 trial results has not yet been released, however, data from this retrospective chart review are available in the package insert and provide insights into the safety and efficacy of Apelvis for the treatment of PROS.

The primary outcome reported is the proportion of patients who responded to treatment at week 24. Response to treatment for patients included in the EPIK-P1 study was defined as: 1) a reduction in volume of at least 1 lesion of at least 20%, 2) an increase in volume of no more than 20% in any 1 lesion, and 3) no new lesions. Volumes were calculated based on clinician review of the images. Apelvis reported that 74% of participants experienced disease reduction and 27% achieved response by the stated criteria, which was confirmed by a blinded independent central review. 70% of patients who responded remained in remission at 6 months, and 60% of patients who responded remained in response at 12 months.

Apelix is a PI3K inhibitor that slows the progression of existing lesions and prevents the development of new lesions in patients with PROS. Important drug interactions exist with both CYP3A4 inducers and CYP2C9 substrates. Additionally, providers of patients receiving apelvis should be aware of potential adverse effects, including hypersensitivity reactions, serious cutaneous adverse reactions, hyperglycemia, pneumonitis, diarrhea, and embryo-fetal toxicity. Despite potential adverse events, current literature demonstrates that apelvis provides clinical benefit to many patients with PROS.