Original Study| Volume 12, ISSUE 6, P428-432, December 2014

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Activity of Cabazitaxel After Docetaxel and Abiraterone Acetate Therapy in Patients With Castration-Resistant Prostate Cancer



      Cabazitaxel and AA have been approved by the US Food and Drug Administration for use after docetaxel in mCRPC. Recently, CAB appeared to be active when given after AA. AA is capable of inducing AR splice variants that confer ligand-independent AR transactivation. Because microtubule-targeting agents impair AR nuclear transport and activity, we raised concerns about CAB efficacy after AA failure in mCRPC.

      Patients and Methods

      One hundred thirty mCRPC patients received AA after docetaxel treatment in compassionate programs. Of them, 24 (18.4%) subsequently received CAB. We retrospectively reviewed their data using conventional methods.


      Twenty-four patients received a median of 4 (range, 1-13) CAB cycles. Nineteen (79.1%) of them received primary prophylaxis with growth factors. Median patient characteristics were: age 65 (range, 57-85) years; Gleason score: 8 (range, 6-10); and PSA: 128.1 (range, 0.01-1700) ng/mL. A PSA response (≥ 50% decrease from baseline) occurred in 6 (31.5%) of 19 evaluable patients (95% confidence interval [CI], 11.8-54.2%). CAB therapy obtained a partial response in 2 of the 13 (15.3%) evaluable patients (95% CI, 2.9-45.4%). Median survival from initiation of CAB was 8.2 (95% CI, 3.34-13.05) months, from AA 16.1 (95% CI, 11.56-20.64) and from docetaxel 32.0 (95% CI, 11.56-39.69).


      A limited number of patients with mCRPC received CAB after docetaxel and AA treatment. In this selected population, CAB was active.


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        • de Bono J.S.
        • Logothetis C.J.
        • Molina A.
        • et al.
        Abiraterone and increased survival in metastatic prostate cancer.
        N Engl J Med. 2011; 364: 1995-2005
        • de Bono J.S.
        • Oudard S.
        • Ozguroglu M.
        • et al.
        Prednisone plus cabazitaxel or mitoxantrone for metastatic castration-resistant prostate cancer progressing after docetaxel treatment: a randomised open-label trial.
        Lancet. 2010; 376: 1147-1154
        • Scher H.I.
        • Fizazi K.
        • Saad F.
        • et al.
        Increased survival with enzalutamide in prostate cancer after chemotherapy.
        N Engl J Med. 2012; 367: 1187-1197
        • Ryan C.J.
        • Smith M.R.
        • de Bono J.S.
        • et al.
        Abiraterone in metastatic prostate cancer without previous chemotherapy.
        N Engl J Med. 2013; 368: 138-148
        • Beer T.M.
        • Armstrong A.J.
        • Sternberg C.
        • et al.
        Enzalutamide in men with chemotherapy-naïve metastatic prostate cancer (mCRPC): results of phase III PREVAIL study.
        J Clin Oncol. 2014; 32 (abstract LBA1)
      1. Jones RJ. Sequencing systemic therapies in advanced prostate cancer: spoiled for choice but not for evidence. Eur Urol, Published online January 2, 2014;

        • Sartor O.
        • Gillessen S.
        Treatment sequencing in metastatic castrate-resistant prostate cancer.
        Asian J Androl. 2014; 16: 426-431
        • Mostaghel E.A.
        • Marck B.T.
        • Plymate S.R.
        • et al.
        Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: induction of steroidogenesis and androgen receptor splice variants.
        Clin Cancer Res. 2011; 17: 5913-5925
        • Efstathiou E.
        • Titus M.
        • Tsavachidou D.
        • et al.
        Effects of abiraterone acetate on androgen signaling in castrate-resistant prostate cancer in bone.
        J Clin Oncol. 2011; 30: 637-643
        • Kuroda K.
        • Liu H.
        • Kim S.
        • Guo M.
        • Navarro V.
        • Bander N.H.
        Docetaxel down-regulates the expression of androgen receptor and prostate-specific antigen but not prostate-specific membrane antigen in prostate cancer cell lines: implications for PSA surrogacy.
        Prostate. 2009; 69: 1579-1585
        • Thadani-Mulero M.
        • Nanus D.M.
        • Giannakakou P.
        Androgen receptor on the move: boarding the microtubule expressway to the nucleus.
        Cancer Res. 2012; 72: 4611-4615
        • Oudard S.
        • Mercier F.
        • Flechon A.
        • et al.
        Efficacy of cabazitaxel and its relationship with predictors of poor response to second hormonal therapies (2d HT) in metastatic castration-resistant prostate cancer (mCRPC).
        J Clin Oncol. 2013; 31 (abstract 137)
        • Mezynski J.
        • Pezaro C.
        • Bianchini D.
        • et al.
        Antitumour activity of docetaxel following treatment with the CYP17A1 inhibitor abiraterone: clinical evidence for cross-resistance?.
        Ann Oncol. 2012; 23: 2943-2947
        • Pond G.R.
        • Armstrong A.J.
        • Galsky M.D.
        • et al.
        Efficacy of docetaxel-based chemotherapy following ketoconazole in metastatic castration-resistant prostate cancer: implications for prior therapy in clinical trials.
        Urol Oncol. 2013; 31: 1457-1463
      2. Pezaro CJ, Omlin AG, Altavilla A, et al. Activity of cabazitaxel in castration-resistant prostate cancer progressing after docetaxel and next-generation endocrine agents. Eur Urol, Published online December 17, 2013;

      3. Memorial Sloan Kettering Cancer Center. Prostate Cancer. Prediction Tools. Available at: Accessed April 27, 2014.

        • Eisenhauer E.A.
        • Therasse P.
        • Bogaerts J.
        • et al.
        New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1).
        Eur J Cancer. 2009; 45: 228-247
        • Scher H.I.
        • Halabi S.
        • Tannock I.
        • et al.
        Design and end points of clinical trials for patients with progressive prostate cancer and castrate levels of testosterone: recommendations of the Prostate Cancer Clinical Trials Working Group.
        J Clin Oncol. 2008; 26: 1148-1159
        • Pezaro C.J.
        • Le Moulec S.
        • Albiges L.
        • et al.
        Response to cabazitaxel in CRPC patients previously treated with docetaxel and abiraterone acetate.
        J Clin Oncol. 2013; 31 (abstract 155)
        • Wissing M.D.
        • Coenen J.L.
        • Van den Berg P.
        • et al.
        A retrospective study on cabazitaxel and abiraterone acetate sequential treatment (CAST) in docetaxel treated metastatic castrate-resistant prostate cancer patients.
        Eur Cancer Congr. 2013; (abstract 2904): 411
      4. Mukherji D, Omlin A, Pezaro C, Shamseddine A, de Bono J. Metastatic castration-resistant prostate cancer (CRPC): preclinical and clinical evidence for the sequential use of novel therapeutics. Cancer Metastasis Rev, Published online January 23, 2014. Accessed April 26, 2014.

        • Sonpavde G.
        • Bhor M.
        • Hennessy D.
        • et al.
        Outcomes with different sequences of cabazitaxel and abiraterone acetate following docetaxel in metastatic castration resistant prostate caner (mCRC).
        Eur J Cancer. 2013; 49 (abstract 2905)
      5. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology (NCCN Guideline). Prostate Cancer. Version 2.2014. Available at: Accessed July 13, 2013.

        • Horwich A.
        • Hugosson J.
        • de Reijke T.
        • et al.
        Prostate cancer: ESMO Consensus Conference Guidelines 2012.
        Ann Oncol. 2013; 24: 1141-1162
        • Schnadig I.D.
        • Bhor M.
        • Vogelzang N.J.
        • et al.
        Sequencing of cabazitaxel and abiraterone acetate following docetaxel in metastatic castration-resistant prostate cancer (mCRPC).
        J Clin Oncol. 2013; 31 (abstract 79)