Omission of Chemotherapy in Early-Stage Hormone-Receptor-Positive, HER2-Negative Breast Cancer with Moderate Risk of Recurrence When Treated with Ribociclib

Breast cancer (mammary carcinoma) is a malignant disease of the breast gland tissue characterized by the uncontrolled proliferation of breast gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the stage of the disease, the presence of detectable hormone receptors on the surface of the cancer cells (estrogen receptor- or progesterone receptor-positive) and the presence of the HER2 receptor on the tumor cells. The standard treatment for early-stage hormone receptor-positive, HER2-negative breast cancer consists of surgical removal of the tumor followed by anti-hormone therapy. For patients with an intermediate risk of recurrence, chemotherapy is often recommended in addition, depending on the individual’s risk of recurrence. Previous studies have shown that, in metastatic, hormone receptor-positive, HER2-negative breast cancer, the combination of anti-hormone therapy and the drug ribociclib has improved treatment outcomes. Ribociclib is a so-called CDK4/6 inhibitor designed to slow the growth of cancer cells. The drug is taken as a tablet and is already approved as a combination therapy for the treatment of early-stage hormone receptor-positive, HER2-negative breast cancer with a high risk of recurrence, as well as for metastatic or locally advanced breast cancer.

The goal of this Phase 3 study is to investigate the efficacy and safety of ribociclib plus anti-hormone therapy compared to standard treatment with chemotherapy followed by ribociclib plus anti-hormone therapy. As part of the study, patients will be randomly assigned to one of two groups and treated in parallel groups. In the study arm, patients will receive ribociclib together with anti-hormone therapy, without prior chemotherapy. In the control arm, patients first receive chemotherapy and then ribociclib in combination with anti-hormonal therapy. The study is open-label, meaning that both the patients and the study physicians know which treatment is being administered. As a non-inferiority study, it investigates whether the treatment without chemotherapy is just as effective as the current treatment with chemotherapy, in order to spare patients the side effects of chemotherapy as much as possible. The main goal (primary endpoint) of the study is invasive breast cancer-free survival for up to twelve years—that is, the period during which no invasive breast cancer recurs and no distant metastases develop after the start of treatment.

Women aged 18 and older with early-stage hormone receptor-positive, HER2-negative breast cancer and a moderate risk of recurrence, for whom chemotherapy would be an option, are eligible to participate in this study. Both postmenopausal and premenopausal women are eligible for the study. For premenopausal women, ovarian function must be suppressed with medication. In addition, the tumor must have been completely surgically removed within the 12 weeks prior to randomization, and anti-hormone therapy must be planned for at least five years. Patients must not have previously received neoadjuvant (pre-surgical) chemotherapy since their breast cancer diagnosis, nor any CDK4/6 inhibitors.