Onkológia 1/2017

Ribociclib, inhibitor of cyclin-dependent kinases 4 and 6, in the treatment of HR+/HER2 - advanced breast cancer

Breast cancer is the most common malignant disease in women worldwide, and about two-thirds of patients have hormone positive disease. Inhibition of cyclin-dependent kinases 4 and 6 (CDK4 / 6) belongs to one of the mechanisms that could potentially reverse the resistance to hormonal therapy (HRT), or delay the development of resistance in patients with advanced breast cancer. Improved efficacy in patients with hormone-positive/HER2-negative (HR+/HER2-) advanced breast cancer was demonstrated in phase III clinical trials, when compared with HRT alone, for combination of fulvestrant and anastrozole, palbociclib or ribociclib with letrozole in the first line; and everolimus with exemestane or fulvestrant with palbociclib in the second-line treatment. Palbociclib, selective CDK4/6 inhibitor, was recently registered for the treatment of patients with HR+/HER2- advanced breast cancer in combination with letrozole or fulvestrant. Positive results from phase III study with another selective CDK 4/6 inhibitor ribociclib in combination with letrozole in the first-line treatment have been published and currently phase III clinical study with CDK4/6 inhibitor abemaciclib is ongoing. The optimal treatment sequence in patients with HR+/HER2- advanced breast cancer is currently unknown and one of research priorities is the search for predictive factors that would allow selection of patients with the best benefits from particular therapy.

Keywords: advanced breast cancer, hormonal therapy, resistence to hormonal therapy, CDK4/6 inhibitors