Dr. Neven on the Relationship of Cell Cycle Genes and Outcomes in HR+/HER2– Breast Cancer

Patrick Neven, MD, a gynecologist-oncologist at the University Hospitals Leuven, discusses the association between cell cycle–related genes and outcomes for patients with hormone receptor(HR)–positive/HER2-negative advanced breast cancer treated on the phase 3 MONALEESA-2 (NCT01958021), MONALEESA-3 (NCT02422615), and MONALEESA-7 (NCT02278120) trials.

At the 2022 San Antonio Breast Cancer Symposium, data were presented from a pooled analysis of gene expression using tumor samples from 1139 patients with HR-positive/HER2-negative advanced breast cancer enrolled on the MONALEESA trials that were used to understand how outcomes for these patients may have been related to cell cycle–related genes. Findings showed that progression-free survival (PFS) benefit with ribociclib (Kisqali) plus endocrine therapy was consistent regardless of the CDK4/6 expression ratio or level of expression of CCNE1, CDK2, RB1, combined cell cycle–related genes, E2F gene signatures, RB gene signature, combined DNA-replication genes, or combined proliferation-related genes.

Findings also showed that patients who were treated with the combination of endocrine treatment plus ribociclib did not have tumors that were more aggressive if they were treated through the subsequent agent, Neven explains. Notably, patients treated with the combination were less likely to have chemotherapy as subsequent treatment, Neven notes.

Moreover, the duration of treatment predicted the subsequent treatment for patients in both arms. For example, if patients experienced a shorter PFS, they were more likely to get chemotherapy, Neven says. Conversely, if a patient experienced a longer PFS, they were more likely to get endocrine therapy with or without targeted therapy, Neven continues.

Numerically, patients who were treated with the endocrine therapy plus ribociclib experienced longer durations of treatment with subsequent therapies, unless they received chemotherapy, Neven continues. The group of patients with the longest overall survival (OS) were those who had the combination treatment with ribociclib and endocrine therapy, followed by another CDK4/6 inhibitor or the same CDK4/6 inhibitor, Neven concludes.