Docetaxel and dasatinib or placebo in men with metastatic castration-resistant prostate cancer (READY): a randomised, double-blind phase 3 trial.

Journal Article (Clinical Trial, Phase III;Journal Article;Multicenter Study)

BACKGROUND: Src kinase-mediated interactions between prostate cancer cells and osteoclasts might promote bone metastasis. Dasatinib inhibits tyrosine kinases, including Src kinases. Data suggests that dasatinib kinase inhibition leads to antitumour activity, affects osteoclasts, and has synergy with docetaxel, a first-line chemotherapy for metastatic castration-resistant prostate cancer. We assessed whether dasatinib plus docetaxel in chemotherapy-naive men with metastatic castration-resistant prostate cancer led to greater efficacy than with docetaxel alone. METHODS: In this double-blind, randomised, placebo-controlled phase 3 study, we enrolled men of 18 years or older with chemotherapy-naive, metastatic, castration-resistant prostate cancer, and adequate organ function from 186 centres across 25 countries. Eligible patients were randomly assigned (1:1) via an interactive voice response system to receive docetaxel (75 mg/m(2) intravenously every 3 weeks, plus oral prednisone 5 mg twice daily), plus either dasatinib (100 mg orally once daily) or placebo until disease progression or unacceptable toxicity. Randomisation was stratified by Eastern Cooperative Oncology Group performance status (0-1 vs 2), bisphosphonate use (yes vs no), and urinary N-telopeptide (uNTx) value (<60 μmol/mol creatinine vs ≥60 μmol/mol creatinine). All patients, investigators, and personnel involved in study conduct and data analyses were blinded to treatment allocation. The primary endpoint was overall survival, analysed by intention to treat. The trial is registered with, number NCT00744497. FINDINGS: Between Oct 30, 2008, and April 11, 2011, 1522 eligible patients were randomly assigned to treatment; 762 patients were assigned to dasatinib and 760 to placebo. At final analysis, median follow-up was 19·0 months (IQR 11·2-25·1) and 914 patients had died. Median overall survival was 21·5 months (95% CI 20·3-22·8) in the dasatinib group and 21·2 months (20·0-23·4) in the placebo group (stratified hazard ratio [HR] 0·99, 95·5% CI 0·87-1·13; p=0·90). The most common grade 3-4 adverse events included diarrhoea (58 [8%] patients in the dasatinib group vs 27 [4%] patients in the placebo group), fatigue (62 [8%] vs 42 [6%]), and asthenia (40 [5%] vs 23 [3%]); grade 3-4 pleural effusions were uncommon (ten [1%] vs three [<1%]). INTERPRETATION: The addition of dasatinib to docetaxel did not improve overall survival for chemotherapy-naive men with metastatic castration-resistant prostate cancer. This study does not support the combination of dasatinib and docetaxel in this population of patients. FUNDING: Bristol-Myers Squibb.

Full Text

Duke Authors

Cited Authors

  • Araujo, JC; Trudel, GC; Saad, F; Armstrong, AJ; Yu, EY; Bellmunt, J; Wilding, G; McCaffrey, J; Serrano, SV; Matveev, VB; Efstathiou, E; Oudard, S; Morris, MJ; Sizer, B; Goebell, PJ; Heidenreich, A; de Bono, JS; Begbie, S; Hong, JH; Richardet, E; Gallardo, E; Paliwal, P; Durham, S; Cheng, S; Logothetis, CJ

Published Date

  • December 2013

Published In

Volume / Issue

  • 14 / 13

Start / End Page

  • 1307 - 1316

PubMed ID

  • 24211163

Pubmed Central ID

  • PMC5478530

Electronic International Standard Serial Number (EISSN)

  • 1474-5488

Digital Object Identifier (DOI)

  • 10.1016/S1470-2045(13)70479-0


  • eng

Conference Location

  • England