Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss

作者：de Bono, Johann S.^*; De Giorgi, Ugo; Rodrigues, Daniel Nava; Massard, Christophe; Bracarda, Sergio; Font, Albert; Arranz Arija, Jose Angel; Shih, Kent C.; Radavoi, George Daniel; Xu, Na; Chan, Wai Y.; Ma, Han; Gendreau, Steven; Riisnaes, Ruth; Patel, Premal H.; Maslyar, Daniel J.; Jinga, Viorel

来源：Clinical Cancer Research, 2019, 25(3): 928-936.

DOI：10.1158/1078-0432.CCR-18-0981

• INHIBITOR
• RISK
• EXPRESSION
• SURVIVAL
• GDC-0068
• PATHWAY

Purpose: PI3K-Akt-mTOR and androgen receptor (AR) signaling are commonlyaberrantly activated in metastatic castration-resistant prostate cancer (mCRPC), with PTEN loss associating with poor prognosis. We therefore conducted a phase Ib/II study of the combination of ipatasertib, an Akt inhibitor, with the CYP17 inhibitor abiraterone in patients with mCRPC. @@@ 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.

• 出版日期2019-2-1