For patients with metastatic hormone receptor (HR)-positive, HER2-negative breast cancer, treatment with a cyclin dependent kinase 4/6 (CDK 4/6) inhibitor in combination with endocrine therapy is a highly effective treatment option. Three CDK4/6 inhibitors are currently approved in the United States in this setting. At the ESMO Congress 2019, final results from the MONARCH 2 and MONALEESA-3 trials, which evaluated the CDK4/6 inhibitors abemaciclib and ribociclib, were presented supporting the overall survival (OS) benefit of this treatment approach. Previous results from both studies established a significant progression-free survival (PFS) advantage for combination CDK4/6 inhibitor and endocrine therapy, supporting the approval of these agents in the first-line setting.
The MONARCH 2 trial, presented by George Sledge, MD (Stanford University, Stanford, California, United States), and simultaneously published in JAMA Oncology, compared the combination of abemaciclib and fulvestrant to fulvestrant alone in 669 patients with HR-positive/HER2-negative breast cancer. Importantly, patients were included on this trial regardless of menopausal status. At a median follow-up of 47.7 months, the median OS significantly favored combination abemaciclib and fulvestrant compared to fulvestrant alone (46.7 months vs 37.3 months; HR 0.757, P = .0137). Updated PFS data demonstrated a continued PFS benefit for the abemaciclib combination, corresponding to a 44% reduction in the risk of progression or death (16.9 months vs 9.3 months; HR 0.56, P < .0001).
Similarly, the MONALEESA-3 trial, presented by Dennis Slamon, MD, PhD (University of California, Los Angeles, California, United States), compared the combination of ribociclib and fulvestrant to fulvestrant alone in 726 postmenopausal patients with HR-positive/HER2-negative metastatic breast cancer. At a median follow-up of 39.4 months, the median OS had not been reached in the ribociclib plus fulvestrant arm, compared to 30.0 months in the fulvestrant alone arm (HR 0.724, P = .00455). Updated PFS data showed continued PFS benefit for ribociclib plus fulvestrant compared to fulvestrant alone (20.6 months vs 12.8 months; HR 0.587).
The authors of these studies concluded that results from both trials provide additional support for the combination of CDK4/6 inhibitor and endocrine therapy as a treatment standard for first-line treatment of HR-positive/HER2-negative advanced breast cancer. Furthermore, these studies validate the efficacy of CDK4/6 inhibitors as a treatment regardless of prior treatment, menopausal status, endocrine sensitivity, and site of metastases.