Abstract PS1-10-05: Efficacy and Safety of PI3K Inhibitors in Hormone Receptor Positive, HER 2 Negative Advanced Breast Cancer: A Meta-Analysis of Phase III Randomized Controlled Trials

Abstract Background: Phosphatidylinositol 3-kinase (PI3K) inhibitors target the phosphoinositide 3-kinase pathway, which is crucial for cell growth, survival, and proliferation. The efficacy of PI3K inhibitors in Hormone receptor -positive, HER 2 – negative advanced breast cancer is an area of active investigation. While promising, concerns about safety, and side effects remain. This study aims to analyze the current data on the safety and efficacy of PI3K inhibitors. Methods: PubMed, Embase and Cochrane database were systematically searched for randomized controlled trials (RCTs) phase III comparing PI3K inhibitors plus standard of care to placebo plus standard of care along in patients with hormone receptor-positive, HER2-negative advanced breast cancer. Studies reporting outcomes such as progression-free survival (PFS), overall survival (OS), response rates (RR), clinical benefit rate (CBR), and adverse events (AEs) were included. A random-effects model was used to synthesize pooled hazard ratio (HR)/risk ratio (RR) with 95% confidence intervals (CIs). Results: Five phase III RCTs with 2992 patients were identified, with 1650 (55.1%) receiving PI3K inhibitors. The pooled Hazard ratio (HR) for PFS was statistically significant in PI3K inhibitors group (HR 0.74; 95% CI 0.68-0.81; p<0.00001, I2 0%), with similar results were seen in PI3K-pathway-activated population (HR 0.57;95%CI 0.47-0.68; p<0.00001, I2 52%). Overall survival (OS) analysis was not statistically significant between the groups (HR 0.89;95% CI 0.79-1.00; p 0.06; I2 0%). Overall response rate (ORR) analysis and Clinical benefit rate (CBR) were higher in PI3K inhibitors group (RR 2.57; 95% CI 1.84-3.58; p< 0.00001; I2 36%), (RR 1.62; 95% CI 1.38-1.91; p<0.00001, I2 63%) respectively. The most frequently observed all-grade adverse events (AEs) in patients treated with PI3K inhibitors were hyperglycemia (50.7 %), diarrhea (44.6%), nausea (34.8%), rash (32.4%), and stomatitis (28.9%). The most common grade 3 or more toxicities were hyperglycemia (16.5%), diarrhea (5.8%), and rash (4.1%). Conclusion: PI3K inhibitors demonstrate a favorable efficacy profile but associated with notable toxicity. Future research is needed to refine their clinical application, maximize therapeutic benefits and optimize their safety profile. Citation Format: S. Albagoush, T. Agarwal, Z. Coy, K. Mohanraj, Y. Elmasry, D. Masih, P. Silberstein. Efficacy and Safety of PI3K Inhibitors in Hormone Receptor Positive, HER 2 Negative Advanced Breast Cancer: A Meta-Analysis of Phase III Randomized Controlled Trials [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS1-10-05.