New drug (name: AZD9833) for the treatment of hormone receptor-positive advanced breast cancer

Breast cancer (mammary carcinoma) is a malignant disease of the mammary gland tissue characterized by the uncontrolled proliferation of mammary gland cells. Treatment of the disease depends on numerous factors, such as the patient’s overall health, the tumor’s growth rate (Ki-67 index), detectable hormone receptors on the surface of the cancer cells (estrogen receptor-positive, progesterone receptor-positive), and the increased presence of the HER2 protein on the cells (HER2-positive). If none of these receptors are present, the cancer is referred to as triple-negative breast cancer. The stage of the disease is also very important: while in the locally confined stage (stages 1–2A) the disease is limited to the breast and a cure is highly likely, the locally advanced stage (stages 2B–3B) indicates that the tumor is already larger or that lymph nodes are involved. In Stage 4, metastases are present, meaning the tumor has spread throughout the body; a cure is highly unlikely at this stage. Various therapies are used to try to “keep the disease in check” for as long as possible. Cancer cells often have a hormone receptor, making hormone therapy a core element of treatment. Among other drugs, aromatase inhibitors (e.g., the already approved anastrozole or letrozole) are used for this purpose. The mechanism of action here is that hormone production in the body is suppressed, thereby “depriving” the tumor of the hormone. AZD9833 is a novel drug that directly destroys the hormone receptor without affecting hormone levels in the body. Since the effectiveness of hormone therapy can often diminish over the course of the disease due to changes in the tumor cells, hormone therapy is now frequently combined directly with a CDK4/6 inhibitor. CDK4/6 inhibitors slow the growth of malignant cells; drugs already approved include palbociclib, abemaciclib, and ribociclib, among others.

The goal of this Phase 3 study is to investigate whether a combination of AZD9833 with a CDK inhibitor is more effective than a conventional aromatase inhibitor combined with a CDK inhibitor, when treatment with an aromatase inhibitor in combination with a CDK inhibitor has already been ongoing for at least 6 months. Participants will be randomly assigned to one of two groups as part of the study. Group 1 will receive AZD9833 + a CDK inhibitor (palbociclib, abemaciclib, or ribociclib). Group 2 receives an aromatase inhibitor + CDK inhibitor. AZD9833 and the aromatase inhibitor are taken daily in tablet form as part of 28-day cycles, and the CDK inhibitors are taken from Day 1 through Day 21. Men and premenopausal women will also receive a monthly subcutaneous injection of a medication to increase estrogen and testosterone production. This is a double-blind study, meaning that neither the medical staff nor the patient knows which medications are being administered. The treatments and follow-up examinations as part of the study will initially take place for approximately 2 years; further follow-up examinations will continue for up to 5 years, during which the effectiveness of the therapy and the occurrence of side effects from the various medications will be evaluated.

Women and men aged 18 and older with hormone receptor-positive, HER2-negative breast cancer are eligible to participate in this study. The disease must involve a mutation in the ESR1 gene, and patients must have already been receiving combination therapy with an aromatase inhibitor and a CDK inhibitor for at least 6 months.