Application of PI3K inhibitors in breast cancer treatment: a clinical trial landscape analysis based on clinical trial databases and registries.

Objective: To characterize the clinical trial landscape of PI3K inhibitors in breast cancer and evaluate their efficacy, safety, and publication status. Methods: We searched eight major clinical trial databases using standardized MeSH/Emtree terms up to January 1, 2026. Of 283 potentially eligible studies screened independently by two reviewers, 87 trials were included for descriptive statistical analysis using R 4.5.1 and SPSS 26.0. Inter-rater agreement was assessed using Cohen's kappa. Results: The United States led global research activity, Europe formed a collaborative network, and China and Korea emerged as important nodes in the Asia-Pacific region. Phase I trials accounted for 34.5% of included studies. PI3Kα was the predominant target (46 trials), and alpelisib was the most extensively studied agent. Marked publication bias was observed, with over 60% of trials involving key targets remaining unpublished; phase I trials had the lowest reporting rate. PI3Kα inhibitors, particularly alpelisib and inavolisib, combined with endocrine therapy improved progression-free survival in PIK3CA-mutated HR+/HER2- advanced breast cancer, while alpelisib was the only agent to demonstrate an overall survival benefit. Pan-PI3K inhibitors showed more limited efficacy and greater toxicity. Hyperglycemia and diarrhea were the most commonly reported serious adverse events. Conclusion: PI3Kα inhibitors show promising efficacy in PIK3CA-mutated HR+/HER2- breast cancer, but publication bias, resistance, target-specific toxicity, and geographic disparities remain major barriers. Mandatory trial reporting, biomarker-guided treatment, and international collaboration should be prioritized.