CDK 4/6 inhibitors have revolutionized treatment for women with HER2-negative, hormone receptor-positive advanced breast cancer. A new study in The Lancet Oncology adds a new group that can benefit from these agents.

The Spanish CORALLEEN study demonstrated that combining the CDK 4/6 inhibitor ribociclib with letrozole reduces the risk of recurrence in high-risk patients with early stage luminal B breast cancer as well as standard chemotherapy with doxorubicin and cyclophosphamide plus paclitaxel.

Cancer cell. Source: Getty

All 106 patients in the study had stage I-IIIA HR+, HER2- luminal B with primary tumor size of at least 2 cm. Patients were randomly assigned on a one:one basis to receive neoadjuvant chemotherapy or the ribociclib combination. At baseline, 92 patients had breast cancer determined to be at high risk of recurrence based on PAM50 analysis. Of the 54 in the chemotherapy arm, 48 were high risk and eight had intermediate risk of recurrence. Among the 52 patients in the ribociclib arm, 44 were high risk and six were intermediate risk.

The researchers followed the participants for 200 days. At the time of surgery, 23 of the 49 patients in the ribociclib group and 24 of the 52 patients in the chemotherapy group were at low risk of recurrence. 

The research team concluded that “some patients with high-risk, early stage, hormone receptor-positive, HER2-negative breast cancer could achieve molecular downstaging  of their disease with CDK4/6 inhibitor and endocrine therapy.”

The most common grade 3 or 4 adverse events in the chemotherapy group were neutropenia, which affected 60% of patients, and febrile neutropenia, which affected 13%. In the ribociclib group, the most common grade 3 or 4 adverse events were neutropenia, affecting 43%, and elevated alanine aminotransferase concentrations, affecting 20% of patients.