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

Autor:	de Bono JS; The Royal Marsden/Institute of Cancer Research, London, United Kingdom. Johann.DeBono@icr.ac.uk., De Giorgi U; Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori, (IRST) IRCCS, Meldola, Italy., Rodrigues DN; The Royal Marsden/Institute of Cancer Research, London, United Kingdom., Massard C; Institut Gustave Roussy, Villejuif, France., Bracarda S; Medical Oncology, Ospedale San Donato, Azienda USL Toscana Sud-Est, Istituto Toscano Tumori, Arezzo, Italy., Font A; Institut Català d'Oncologia, Hospital Germans Trias i Pujol, Badalona, Spain., Arranz Arija JA; Hospital General Universitario Gregorio Marañón, Madrid, Spain., Shih KC; Tennessee Oncology, Nashville, Tennessee., Radavoi GD; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania., Xu N; Genentech, Inc., South San Francisco, California., Chan WY; Genentech, Inc., South San Francisco, California., Ma H; Genentech, Inc., South San Francisco, California., Gendreau S; Genentech, Inc., South San Francisco, California., Riisnaes R; The Royal Marsden/Institute of Cancer Research, London, United Kingdom., Patel PH; Genentech, Inc., South San Francisco, California., Maslyar DJ; Genentech, Inc., South San Francisco, California., Jinga V; Carol Davila University of Medicine and Pharmacy, Bucharest, Romania.
Jazyk:	angličtina
Zdroj:	Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2019 Feb 01; Vol. 25 (3), pp. 928-936. Date of Electronic Publication: 2018 Jul 23.
DOI:	10.1158/1078-0432.CCR-18-0981
Abstrakt:	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 . (©2018 American Association for Cancer Research.)
Databáze:	MEDLINE
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