Patients and Methods: Patients were randomized 1:1:1 to ipatasertib 400 mg, ipatasertib 200 mg, or placebo, with abiraterone 1,000 mg orally. Coprimary efficacy endpoints were radiographic progression-free survival (rPFS) in the intent-to-treat population and in patients with PTEN-loss tumors.
Results: rPFS was prolonged in the ipatasertib cohort versus placebo, with similar trends in overall survival and time-to-PSA progression. A larger rPFS prolongation for the combination was demonstrated in PTEN-loss tumors versus those without. The combination was well tolerated, with no treatment-related deaths.
Conclusions: In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors.
Johann S. de Bono, Ugo De Giorgi, Daniel Nava Rodrigues, Christophe Massard, Sergio Bracarda, Albert Font, Jose Angel Arranz Arija, Kent C. Shih, George Daniel Radavoi, Na Xu, Wai Y. Chan, Han Ma, Steven Gendreau, Ruth Riisnaes, Premal H. Patel, Daniel J. Maslyar and Viorel Jinga
J de Bono et al. Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss,
Clin Cancer Res February 1 2019 (25) (3) 928-936; DOI: 10.1158/1078-0432.CCR-18-0981