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.
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.
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, and potential intrapatient heterogeneity.
Ipatasertib addition to abiraterone did not improve OS for men with mCRPC, regardless of PTEN status on IHC. Exploratory biomarker analyses identified additional genomic alterations of potential clinical relevance for AKT blockade in mCRPC that require further validation in prospective studies.
European urology. 2025 Jan 29 [Epub ahead of print]
Johann S de Bono, Meng He, Zhen Shi, Malgorzata Nowicka, Sergio Bracarda, Cora N Sternberg, Kim N Chi, David Olmos, Shahneen Sandhu, Christophe Massard, Nobuaki Matsubara, Geng Chen, Nives Selak Bienz, Daniel Canter, Matthew Wongchenko, Christopher Sweeney
Institute of Cancer Research and Royal Marsden Hospital London UK., Genentech South San Francisco CA USA., F. Hoffmann-La Roche Basel Switzerland., Azienda Ospedaliera Santa Maria Terni Italy., Englander Institute for Precision Medicine, Weill Cornell Medicine, Meyer Cancer Center, NewYork-Presbyterian New York NY USA., BC Cancer Vancouver Canada., Instituto de Investigación Sanitaria, Hospital Universitario 12 de Octubre Madrid Spain., Peter MacCallum Cancer Centre and University of Melbourne Melbourne Australia., Institut Gustave Roussy Villejuif France., National Cancer Center Hospital East Chiba Japan., South Australian Immunogenomics Cancer Institute, University of Adelaide Adelaide Australia. Electronic address: .