Work

Impact of PIK3CA Mutations on the Clinical Benefits of CDK 4/6 Inhibitors in HR+/HER2- Advanced Breast Cancer: An Updated Pairwise and Network Meta-Analysis

Year: 2025

Type: article

Study designs: Systematic Review, Meta-Analysis

Abstract: Background: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone receptor-positive (HR+) and human epidermal growth factor receptor-2 negative (HER2-) advanced breast cancer.However, identifying reliable biomarkers and determining overall survival (OS) outcomes for CDK4/6i remains challenging.Methods: We conducted a systematic review and updated pairwise meta-analysis of randomized controlled trials to evaluate the clinical benefits and biomarker interactions of CDK4/6i in HR+ and HER2-advanced breast cancer.Hazard ratio (HR) and 95% confidence interval (CI) were calculated for progression-free survival (PFS) and OS across different clinical settings.Additionally, a network meta-analysis was performed to assess the comparative efficacy of different CDK4/6i in specific populations using ranking probabilities.Results: CDK4/6i significantly improved PFS (HR 0.55, 95% CI 0.52-0.59)and OS (HR 0.80, 95% CI 0.74-0.86) in patients with HR+/HER2-advanced breast cancer.Sensitivity analyses confirmed the robustness of these findings.Subgroup and meta-regression analyses demonstrated consistent clinical benefits across different lines of therapy, endocrine therapy categories, patient characteristics, and follow-up durations.However, PIK3CA mutation status emerged as a potential CDK4/6i efficacy modifier, particularly among patients who were endocrine therapy-naïve for advanced disease (First-line treatment: p for interaction = 0.03; received prior treatment, p = 0.68).The network meta-analysis suggested comparable overall efficacy among CDK4/6i.Ivyspring

Source: Journal of Cancer

DOI: 10.7150/jca.111362