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|Ref Type||Journal Article|
|Authors||de Bono JS, De Giorgi U, Rodrigues DN, Massard C, Bracarda S, Font A, Arranz Arija JA, Shih KC, Radavoi GD, Xu N, Chan WY, Ma H, Gendreau S, Riisnaes R, Patel PH, Maslyar DJ, Jinga V|
|Title||Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss.|
|Journal||Clinical cancer research : an official journal of the American Association for Cancer Research|
|Date||2019 Feb 01|
|Abstract Text||PI3K-Akt-mTOR and androgen receptor (AR) signaling are commonly aberrantly 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.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.In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors.See related commentary by Zhang et al., p. 901.|
|Molecular Profile||Treatment Approach|
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|PTEN loss||castration-resistant prostate carcinoma||sensitive||Abiraterone + Ipatasertib||Phase II||Actionable||In a Phase II trial, the combination of Ipatasertib (GDC-0068) and Zytiga (abiraterone) resulted in a better progression-free survival in metastatic castration resistant prostate cancer patients with PTEN loss (by IHC) when compared to placebo combined with Zytiga (PMID: 30037818; NCT01485861).||30037818 detail...|