Final Overall Survival and Molecular Data Associated with Clinical Outcomes in Patients Receiving Ipatasertib and Abiraterone in the Phase 3 IPATential150 Trial

作者：Johann S. de Bono, He Meng, Zhen Shi, Małgorzata Nowicka, Sergio Bracarda, Cora N. Sternberg, Kim N., David Olmos, Shahneen Sandhu, Christophe Massard, Nobuaki Matsubara, Geng Chen, Nives Selak Bienz, Daniel Canter, Matthew Wongchenko, Christopher J. Sweeney · 发表于：European Urology · 年份：2025 · DOI：10.1016/j.eururo.2024.12.015 · 被引用次数：24 · 研究领域：Prostate Cancer Treatment and Research、PI3K/AKT/mTOR signaling in cancer、Prostate Cancer Diagnosis and Treatment

BACKGROUND AND OBJECTIVE: In the phase 3 IPATential150 trial, ipatasertib addition to abiraterone significantly reduced the risk of disease progression in men with metastatic castration-resistant prostate cancer (mCRPC) with PTEN loss on immunohistochemistry (IHC), but not in the intention-to-treat (ITT) population. Here we report the final overall survival (OS) analysis and present results for prespecified and exploratory biomarker analyses. METHODS: Patients were randomized to receive ipatasertib (400 mg once daily) or placebo. All patients received abiraterone (1000 mg once daily) and prednisone (5 mg twice daily). OS was assessed in patients with PTEN loss on IHC and the ITT population. Exploratory biomarker analyses included PTEN status via next-generation sequencing (NGS) and other key genomic alterations. KEY FINDINGS AND LIMITATIONS: At final analysis (median follow-up 33.9 mo), ipatasertib addition did not improve OS for patients with PTEN loss in IHC (n = 521; stratified hazard ratio [sHR] 0.94, 95% confidence interval [CI] 0.76-1.17; p = 0.57) or the ITT population (n = 1101; sHR 0.91, 95% CI 0.79-1.07; not formally tested). Exploratory NGS assessments identified subgroups with genomic PTEN loss (n = 208) or PIK3CA/AKT1/PTEN alterations (n = 250), with potentially better outcomes from ipatasertib (HR 0.76, 95% CI 0.54-1.07; and HR 0.70, 95% CI 0.51-0.96, respectively). Limitations include the exploratory nature of the analysis, incomplete availability of NGS data, ...