Gedatolisib as a new drug in combination with established drugs compared with standard treatment for advanced or metastatic hormone receptor-positive, HER2-negative breast cancer (VICTORIA-1)

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue characterized by the uncontrolled proliferation of breast cells. In advanced stages, or when breast cancer has already spread to other parts of the body (metastases), the disease is often no longer curable. In such cases, the goal is to “keep the disease in check” for as long as possible. If the cancer cells are hormone receptor-positive, anti-hormone therapy is recommended as standard treatment. Fulvestrant is a medication used to treat hormone receptor-positive breast cancer in postmenopausal women. It belongs to the group of selective estrogen receptor degraders (SERDs). Anti-hormonal therapy is often combined with a CDK4/6 inhibitor, as this increases the effectiveness of the anti-hormonal therapy.

Gedatolisib is a novel drug that has not yet been officially approved. It binds to various tumor proteins and prevents the tumor from growing. One target enzyme is phosphoinositide-3 kinases (PIK3), which, in earlier studies, have already been linked to a poorer prognosis when altered by cancer. Targeted inhibition—for example, with the drug alpelisib—has demonstrated a survival benefit in studies.

The goal of the VICTORIA-1 study is to test gedatolisib in various drug combinations, taking into account whether a PIK3CA mutation is present in the tumor cells.

The trial has a total of 6 study arms, with 3 groups requiring a PIK3CA mutation and the other 3 not. Patients without the mutation receive the new drug gedatolisib in combination with fulvestrant, with or without the CDK4/6 inhibitor palbociclib, compared to standard therapy with fulvestrant alone. If a PIK3CA mutation is detected, one group receives gedatolisib in combination with fulvestrant, and the second group receives gedatolisib + palbociclib + fulvestrant. The third group is the standard-of-care group, which receives fulvestrant in combination with alpelisib. Assignment to treatment groups is randomized based on the determination of PIK3CA status. This Phase 3 trial is collecting data to support the potential approval of gedatolisib. To date, the drug has not yet been approved in Germany outside of clinical trials. Gedatolisib is administered once weekly in a 3-week cycle. The total duration of treatment depends on the individual’s response to therapy. Follow-up as part of the study will continue for approximately 48 months.

Women and men aged 18 and older with hormone receptor-positive, HER2-negative breast cancer at the locally advanced stage (stages 2B to 3) or metastatic stage (stage 4) are eligible to participate in the study. The disease must have progressed during first-line therapy with aromatase inhibitors, and the patient must have already received treatment with a CDK4/6 inhibitor. Brain metastases may lead to exclusion, as may insufficient kidney, liver, or heart function. In addition, life expectancy must be more than three months. Patients must not have previously received treatment with a PIK3 inhibitor. PIK3CA status will be assessed as part of the study.