To determine whether a new anti-hormone therapy using the new drug giredestrant can improve survival in patients with advanced or metastatic estrogen receptor-positive breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue in which malignant cells multiply uncontrollably. In estrogen receptor-positive breast cancer, estrogen promotes tumor growth. If estrogen receptors and/or progesterone receptors are detectable on the breast cancer cells, the cancer is referred to as hormone receptor-positive, which is of great importance for the treatment strategy. Standard treatment involves surgery, chemotherapy, and/or radiation therapy, followed by anti-hormone therapy to suppress any remaining cancer cells. However, tumor cells sometimes develop mutations in the estrogen receptor, making them resistant to anti-hormone therapies. In such cases, a cyclin-dependent kinase 4/6 inhibitor (CDK4/6 inhibitor) such as palbociclib, ribociclib, or abemaciclib is often used in combination with fulvestrant. Fulvestrant blocks the estrogen receptor but must be administered monthly via injection and has limited efficacy in cases of estrogen receptor mutations. Giredestrant is a newly developed oral medication that blocks the estrogen receptor and may also be more effective in cases of receptor mutations.

In the pionERA study, patients are randomly assigned to one of two treatment groups: Group 1 receives giredestrant (daily tablets) plus a CDK4/6 inhibitor selected by the study physicians (palbociclib, ribociclib, or abemaciclib). Group 2 receives fulvestrant (injections at the start and then monthly) in combination with a CDK4/6 inhibitor. Treatment is administered in 28-day cycles and continues until the disease progresses or adverse side effects occur. The study is an open-label, randomized trial, meaning that patients are randomly assigned to one of the two treatment groups. Both the patients and the medical staff know which group they have been assigned to. The effect of the treatment will be monitored for up to 5 years.

Eligible participants include adult women and men with advanced breast cancer that cannot be surgically removed or has metastasized and no longer responds to prior anti-hormone therapy. Participation is only possible if no prior systemic treatment (chemotherapy) has been administered for the advanced disease. The tumor must be estrogen receptor-positive and HER2-negative.