Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss
Mené sur des patients atteints d'un cancer de la prostate de stade métastatique, cet essai de phase Ib/II évalue l'efficacité, du point de vue de la survie sans progression, d'un traitement combinant ipatasertib, un inhibiteur de Akt, et abiratérone, un inhibiteur de CYP17, selon la perte d'expression de la protéine PTEN
Purpose: 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. Experimental Design: 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. Clin Cancer Res; 1–9. ©2018 AACR.