CDK4/6 Inhibition in the Management of Metastatic HR+/HER2+ Breast Cancer: Systematic Review and Meta-analysis

Hormone receptor-positive/human epidermal growth factor receptor 2-positive (HR+/HER2+) breast cancer accounts for approximately 10% of breast cancer cases and is associated with therapeutic resistance and variable clinical outcomes. Preclinical studies suggest that CDK4/6 inhibition may enhance the activity of combined endocrine and HER2-targeted therapy.

To summarize and synthesize available clinical trial evidence evaluating CDK4/6 inhibitors in metastatic HR+/HER2+ breast cancer.

We conducted a systematic review and descriptive meta-analysis of four clinical trials evaluating CDK4/6 inhibitors in combination with endocrine and anti-HER2 therapy in metastatic HR+/HER2+ breast cancer. A random-effects model was used to summarize pooled efficacy outcomes.

The pooled objective response rate was 33%. Complete response occurred in 2% of patients, partial response in 35%, and stable disease in 40%, and the clinical benefit rate was 69%. Substantial heterogeneity was observed across studies.

Across available clinical trials, CDK4/6 inhibitor-based combination therapy was associated with disease control in a subset of patients with metastatic HR+/HER2+ breast cancer. Given the heterogeneity of study designs and limited comparative data, these findings should be interpreted cautiously and support the need for further randomized trials to better define optimal treatment strategies and patient selection.