Randomized Phase II Study Evaluating Akt Blockade with Ipatasertib, in Combination with Abiraterone, in Patients with Metastatic Prostate Cancer with and without PTEN Loss
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- Johann S. de Bono
- 1The Royal Marsden/Institute of Cancer Research, London, United Kingdom.
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- Ugo De Giorgi
- 2Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, (IRST) IRCCS, Meldola, Italy.
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- Daniel Nava Rodrigues
- 1The Royal Marsden/Institute of Cancer Research, London, United Kingdom.
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- Christophe Massard
- 3Institut Gustave Roussy, Villejuif, France.
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- Sergio Bracarda
- 4Medical Oncology, Ospedale San Donato, Azienda USL Toscana Sud-Est, Istituto Toscano Tumori, Arezzo, Italy.
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- Albert Font
- 5Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain.
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- Jose Angel Arranz Arija
- 6Hospital General Universitario Gregorio Marañón, Madrid, Spain.
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- Kent C. Shih
- 7Tennessee Oncology, Nashville, Tennessee.
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- George Daniel Radavoi
- 8Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
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- Na Xu
- 9Genentech, Inc., South San Francisco, California.
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- Wai Y. Chan
- 9Genentech, Inc., South San Francisco, California.
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- Han Ma
- 9Genentech, Inc., South San Francisco, California.
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- Steven Gendreau
- 9Genentech, Inc., South San Francisco, California.
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- Ruth Riisnaes
- 1The Royal Marsden/Institute of Cancer Research, London, United Kingdom.
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- Premal H. Patel
- 9Genentech, Inc., South San Francisco, California.
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- Daniel J. Maslyar
- 9Genentech, Inc., South San Francisco, California.
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- Viorel Jinga
- 8Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
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<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Purpose:</jats:title> <jats: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.</jats:p> <jats:p>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.</jats:p> </jats:sec> <jats:sec> <jats:title>Results:</jats:title> <jats: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.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions:</jats:title> <jats:p>In mCRPC, combined blockade with abiraterone and ipatasertib showed superior antitumor activity to abiraterone alone, especially in patients with PTEN-loss tumors.</jats:p> <jats:p>See related commentary by Zhang et al., p. 901</jats:p> </jats:sec>
収録刊行物
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- Clinical Cancer Research
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Clinical Cancer Research 25 (3), 928-936, 2019-02-01
American Association for Cancer Research (AACR)