Cyclin-dependent kinase 4/6 (CDK4/6) inhibitors in combination with endocrine therapy (ET) have demonstrated a significant improvement in survival outcomes for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). A meta-analysis, encompassing data from 9 randomized controlled trials (RCTs) and 5043 women, has affirmed the efficacy and safety of this combination therapy compared to ET alone. The study, which included data regardless of treatment line, menopausal status, and other individual characteristics, underscores the potential of CDK4/6 inhibitors to reshape the treatment landscape for this patient population.
The meta-analysis, which systematically searched databases including PubMed, Embase, and Cochrane, evaluated progression-free survival (PFS), overall survival (OS), objective response rate (ORR), clinical benefit rate (CBR), and adverse events (AEs). The results indicated a substantial improvement in PFS with the combination therapy (HR 0.54, 95% CI 0.50-0.59, p< 0.00001) compared to ET alone. Furthermore, a significant OS benefit was observed (HR 0.77, 95% CI 0.69-0.85, p< 0.00001), reinforcing the clinical value of this therapeutic approach.
Impact Across Treatment Lines and Menopausal Status
The benefits of CDK4/6 inhibitors plus ET were consistent across different treatment lines for advanced disease. In both first-line and subsequent-line settings, the combination therapy demonstrated superior PFS (HR 0.52, 95% CI 0.46-0.59 in first line) and OS (HR 0.75, 95% CI 0.66-0.85 in first line) compared to ET alone. Similarly, the positive effects were observed regardless of menopausal status, with comparable hazard ratios for PFS (HR 0.54, 95% CI 0.50-0.58) and OS (HR 0.76, 95% CI 0.68-0.84).
Safety Considerations
While the combination therapy demonstrated significant efficacy, the meta-analysis also highlighted an increased risk of grade 3/4 adverse events (RR 2.66, 95% CI 2.44-2.90, p < 0.00001) compared to ET alone. Healthcare professionals should carefully monitor patients receiving CDK4/6 inhibitors plus ET for potential side effects and manage them appropriately.
Implications for Clinical Practice
The findings from this meta-analysis provide strong evidence supporting the use of CDK4/6 inhibitors in combination with ET as a preferred treatment strategy for HR+/HER2- ABC. The consistent benefits observed across various subgroups of patients, coupled with the manageable safety profile, position this combination as a cornerstone of therapy for this prevalent subtype of breast cancer. Further research may focus on identifying predictive biomarkers to optimize patient selection and personalize treatment approaches.
