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Updated: Feb 28, 2026
A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With
Emmanuel S Antonarakis1, Scott T Tagawa1, Giuseppe Galletti1
1Emmanuel S. Antonarakis and Mario A. Eisenberger, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD; Scott T. Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Brian J. Kirby, David M. Nanus, and Paraskevi Giannakakou, Weill Cornell Medicine/Meyer Cancer Center; Che-Kai Tsao, Mount Sinai Medical Center, New York; Timothy B. Lannin, Shalu Suri, Conor N. Gruber, Erica D. Pratt, and Brian J. Kirby, Cornell University, Ithaca, NY; Marie Vanhuyse, Medical Oncology, Montréal General Hospital; Fred Saad, University of Montreal Hospital Center, Montreal; John Stewart, Atef Zaher, and Wei Zhou, Sanofi, Laval, Quebec, Canada; Guru Sonpavde, University of Alabama at Birmingham Comprehensive Cancer Center, Birmingham, AL; Scott North, University of Alberta, Cross Cancer Institute, Edmonton, Alberta, Canada; Costantine Albany, Indiana University School of Medicine, Indianapolis, IN; and Ted Szatrowski, Sanofi, Bridgewater, NJ.
Abstract:
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327). The primary biomarker endpoint was analysis of post-treatment CTCs to confirm the hypothesis that clinical response was associated with taxane drug-target engagement, evidenced by decreased percent androgen receptor nuclear localization (%ARNL) and increased microtubule bundling. Results Sixty-three patients were randomly assigned to docetaxel (n = 41) or cabazitaxel (n = 22); 44.4% received prior potent androgen receptor-targeted therapy. Overall, 35 patients (55.6%) had confirmed ≥ 50% PSA responses, exceeding the historical control rate of 45.4% (TAX327). Of 61 treated patients, 33 (54.1%) had ≥ 30% PSA declines by C4 and did not switch taxane, 15 patients (24.6%) who did not achieve ≥ 30% PSA declines by C4 switched taxane, and 13 patients (21.3%) discontinued therapy before or at C4. Of patients switching taxane, 46.7% subsequently achieved ≥ 50% PSA decrease. In 26 CTC-evaluable patients, taxane-induced decrease in %ARNL (cycle 1 day 1 v cycle 1 day 8) was associated with a higher rate of ≥ 50% PSA decrease at C4 ( P = .009). Median composite progression-free survival was 9.1 months (95% CI, 4.9 to 11.7 months); median overall survival was not reached at 14 months. Common grade 3 or 4 adverse events included fatigue (13.1%) and febrile neutropenia (11.5%). Conclusion The early taxane switch strategy was associated with improved PSA response rates versus TAX327. Taxane-induced shifts in %ARNL may serve as an early biomarker of clinical benefit in patients treated with taxanes.
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