New CDK4 inhibitor atirmociclib (PF-07220060) in combination with letrozole for advanced or metastatic, hormone receptor-positive, HER2-negative breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the breast tissue in which cells in the breast multiply uncontrollably. Treatment depends on various factors, including the patient’s overall health, the stage of the disease, and the biological characteristics of the tumor, such as the presence of hormone receptors (estrogen receptor-positive, progesterone receptor-positive) and HER2 status. In hormone receptor-positive breast cancer, female hormones such as estrogen promote tumor growth, which is why anti-hormone therapy is a central element of treatment. If the disease is advanced or has spread throughout the body (metastasized), anti-hormone therapy is routinely combined with a CDK4/6 inhibitor to slow tumor growth. Approved drugs in this class include palbociclib, ribociclib, and abemaciclib, which are taken as tablets or capsules. Atirmociclib (PF-07220060) is a new drug that specifically inhibits the CDK4 enzyme, which is necessary for the division of cancer cells. Unlike the CDK4/6 inhibitors approved to date, atirmociclib targets CDK4 exclusively and may therefore achieve a more targeted effect while offering better tolerability. The drug has not yet been approved for the treatment of breast cancer.

The goal of the Phase 3 study is to investigate whether atirmociclib (PF-07220060) combined with letrozole is more effective and better tolerated compared to an already approved CDK4/6 inhibitor combined with letrozole. Patients are randomly assigned to two groups. In the study arm, patients receive atirmociclib as a tablet together with the aromatase inhibitor letrozole as a tablet. In the control arm, patients will receive an already approved CDK4/6 inhibitor (palbociclib, ribociclib, or abemaciclib) selected by the study physicians, along with letrozole. The study is open-label (not blinded), meaning that both the patients and the study physicians know which medication is being administered. The primary objective is to determine whether atirmociclib can delay disease progression compared to standard therapy (progression-free survival). In addition, overall survival, response to treatment, tolerability, and quality of life will be assessed. To participate, patients must, among other criteria, have confirmed hormone receptor-positive, HER2-negative breast cancer that is not curable by surgery and must not have previously received systemic cancer therapy for the advanced disease.

Women and men aged 18 and older with advanced or metastatic, hormone receptor-positive, HER2-negative breast cancer who have not previously received systemic cancer therapy for their advanced disease are eligible to participate in this study. The estimated duration of the study is approximately 13 years.