Antonarakis, Emmanuel S.Tagawa, Scott T.Galleti, GiuseppeWorroll, DanielBallman, KarlaVanhuyse, MarieSonpavde, GuruNorth, ScottAlbany, CostantineTsao, Che-KaiStewart, JohnZaher, AtefSzatrowski, TedZhou, WeiGjyrezi, AdaTasaki, ShinsukePortella, LuigiBai, YangLannin, Timothy B.Suri, ShaluGruber, Conor N.Pratt, Erica D.Kirby, Brian J.Eisenberger, Mario A.Nanus, David M.Saad, FredGiannakakou, ParaskeviTAXYNERGY Investigators2018-07-202018-07-202017-10-01Antonarakis, E. S., Tagawa, S. T., Galletti, G., Worroll, D., Ballman, K., Vanhuyse, M., … on behalf of the TAXYNERGY Investigators. (2017). Randomized, Noncomparative, Phase II Trial of Early Switch From Docetaxel to Cabazitaxel or Vice Versa, With Integrated Biomarker Analysis, in Men With Chemotherapy-Naïve, Metastatic, Castration-Resistant Prostate Cancer. Journal of Clinical Oncology, 35(28), 3181–3188. http://doi.org/10.1200/JCO.2017.72.4138https://hdl.handle.net/1805/16753Purpose 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.en-USPublisher PolicyBiomarkers, TumorCell nucleusDisease-free survivalDrug administration scheduleKallikreinsNeoplastic cells, CirculatingProstate-specific antigenReceptors, AndrogenTaxoidsArticle