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Clin Cancer Res. 2019 Feb 1;25(3):928-936. doi: 10.1158/1078-0432.CCR-18-0981. Epub 2018 Jul 23.

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

Author information

1
The Royal Marsden/Institute of Cancer Research, London, United Kingdom. Johann.DeBono@icr.ac.uk.
2
Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, (IRST) IRCCS, Meldola, Italy.
3
The Royal Marsden/Institute of Cancer Research, London, United Kingdom.
4
Institut Gustave Roussy, Villejuif, France.
5
Medical Oncology, Ospedale San Donato, Azienda USL Toscana Sud-Est, Istituto Toscano Tumori, Arezzo, Italy.
6
Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain.
7
Hospital General Universitario Gregorio Marañón, Madrid, Spain.
8
Tennessee Oncology, Nashville, Tennessee.
9
Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
10
Genentech, Inc., South San Francisco, California.

Abstract

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.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.See related commentary by Zhang et al., p. 901.

PMID:
30037818
DOI:
10.1158/1078-0432.CCR-18-0981
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