Can Stage 4 Hormone-Positive Breast Cancer Be Treated Without Chemotherapy?

Successful Results of Abemaciclib Announced at ESMO 2017.

In hormone-positive, Her2 receptor -negative, fourth-stage breast cancer, chemotherapy is currently a frequently preferred treatment. Except in patients with low-volume, meaning limited, metastasis , advanced age or poor general condition, the worldwide treatment preference is to begin with chemotherapy and, in patients doing well and responding, continue with hormonal therapy .

In this patient group, especially without aggressive metastases in organs such as the liver, lungs or brain, chemotherapy has a high side-effect rate and its efficacy is not satisfactory. Over the last three years, highly encouraging scientific developments have occurred for this group, particularly postmenopausal patients with hormone receptor-positive metastatic breast cancer.

Cancer intracellular growth signaling pathways can be targeted by drugs blocking cyclin-dependent kinase 4/6; combining these drugs with hormonal treatments significantly increased treatment success. The first of these drugs, Palbociclib, was initially tested in previously treated, unresponsive patients in the PALOMA 1-3 studies. After successful results, as first-choice treatment in metastatic patients, hormonal therapy was combined with Pablociclib . It received FDA approval based on effective study data strong enough to change routine practice. Following Palbociclib, similar strategies in the MONOLEESA 1-2 studies tested Ribociclib , a cyclin-dependent kinase 4/6 inhibitor. Its successful results made it the second proven effective drug receiving FDA approval in this area in 2017. The third-generation drug Abemaciclib followed similar paths to the first two drugs in MONRCH 1-2 and was found successful; subsequently, at ESMO 2017, the results of the MONARCH 3 study were announced. Postmenopausal breast cancer patients with hormone receptor-positive, Her2 receptor-negative disease, newly diagnosed metastasis and no prior treatment received the well-known and frequently used hormonal drugs Anastrozole and Letrozole , with abemaciclib added in one group and placebo, an inactive drug, in the other. A total of 328 patients received hormonal therapy combined with Abemaciclib, while 165 received conventional hormonal therapy and placebo.

According to the announced preliminary results, Abemaciclib reduced the risk of disease progression by %46. Regression of measurable lesions was %59 in the Abemaciclib arm and %44 in the conventional treatment arm. Side effects were manageable. Compared with the first two cyclin kinase 4/6 inhibitors, Abemaciclib caused more diarrhea but less frequent decreases in blood neutrophil levels (white blood cells, defense cells) than the other drugs. The follow-up duration is not yet sufficient to fully compare time to progression in the Abemaciclib arm and overall survival in the two groups.

World oncology authorities also found this development striking, stating that in this breast cancer group chemotherapy is increasingly giving way to new targeted agents known as targeted drugs.

We will follow and share the long-term results of this study for you.