Abstract
<div>AbstractPurpose:<p>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.</p><p><b>Patients and Methods:</b> 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.</p>Results:<p>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.</p>Conclusions:<p>In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors.</p><p><i>See related commentary by Zhang et al., p. 901</i></p></div>
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