• Nader Al Nakouzi, Sylvestre Le Moulec, Laurence Albigès, Chris Wang, Philippe Beuzeboc, Marine Gross-Goupil, Thibault de La Motte Rouge, Aline Guillot, Dorota Gajda, Christophe Massard, Martin Gleave, Karim Fizazi, and Yohann Loriot.
• Vancouver Prostate Centre, University of British Columbia, Vancouver, British Columbia, Canada.
• Eur. Urol. 2015 Aug 1; 68 (2): 228-35.

BackgroundCabazitaxel, abiraterone acetate (AA), and enzalutamide have been approved for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) following docetaxel chemotherapy. Whether taxanes and next-generation androgen receptor (AR) axis inhibitors are cross-resistant or not is a subject of debate.ObjectiveTo evaluate the antitumour activity of cabazitaxel in mCRPC pretreated with abiraterone or enzalutamide.Design, Setting, And ParticipantsThe antitumour activity of cabazitaxel was assessed in patients with mCRPC and progressive disease after treatment with docetaxel and AA. In parallel, cabazitaxel antitumour activity was studied in enzalutamide-resistant models.Outcome Measurements And Statistical AnalysisChanges in prostate-specific antigen (PSA) levels and progression-free survival were used to determine the activity of cabazitaxel treatment. Cell proliferation, immunofluorescence, and AR transactivation assay were used in enzalutamide-resistant models.Results And LimitationsA total of 79 patients who had progressive mCRPC after docetaxel (median: 8 cycles; range: 4-12 mo), and AA (median: 4.8 mo; range:1-55 mo) received cabazitaxel 25mg/m(2) every 3 weeks (median: 6 cycles; range:1-15 cycles). A PSA decline ≥30% was achieved in 48 patients (62%; 95% confidence interval [CI], 51-73), and a decline ≥50% was achieved in 28 patients (35%; 95% CI, 25-47). The median progression-free survival and overall survival were 4.4 and 10.9 mo, respectively. In vitro, cabazitaxel decreased cell viability in both enzalutamide-sensitive and enzalutamide-resistant prostate cancer cells within the same range of concentrations. PC3, an AR-negative cell line, exhibited similar sensitivity to cabazitaxel.ConclusionsCabazitaxel and AR-pathway inhibitors are not cross-resistant. Preclinical data suggest that cabazitaxel activity does not act mainly through AR axis inhibition.Patient SummaryThe antitumour activity of cabazitaxel, a chemotherapy agent, was studied in prostate cancer resistant to conventional hormonal therapy and to more recent endocrine therapies (abiraterone or enzalutamide). Cabazitaxel retained anticancer activity in more than half of the cases.Copyright © 2014 European Association of Urology. Published by Elsevier B.V. All rights reserved.

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