Early Taxane Switching May Improve PSA Response Rates in Prostate Cancer

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Early switching from docetaxel to cabazitaxel or vice versa may lead to improved prostate-specific antigen response rates.
Early switching from docetaxel to cabazitaxel or vice versa may lead to improved prostate-specific antigen response rates.

Early switching from docetaxel to cabazitaxel or vice versa may lead to improved prostate-specific antigen (PSA) response rates, according to a study published in the Journal of Clinical Oncology.1

The phase 2, randomized, non-comparative TAXYNERGY trial (ClinicalTrials.gov Identifier: NCT01718353) enrolled chemotherapy-naïve patients with metastatic, castration-resistant prostate cancer (mCRPC) to evaluate the clinical benefit of early taxane switch and the usefulness of circulating tumor cells (CTCs) as a biomarker.

Forty-one patients received docetaxel 75mg/m2 and 22 received cabazitaxel 25mg/m2 every 3 weeks plus daily prednisone 10 mg. Patients who did not see at least a 30% PSA decline by cycle 4 (C4; week 12) switched taxanes, and patients who achieved at least a 30% decline in PSA from baseline were maintained on the initial taxane.

The primary clinical endpoint of this study was achieving at least a 50% PSA decline from baseline vs the historical control (TAX327).

The primary biomarker endpoint was to confirm that clinical response rate correlates with drug target engagement (DTE) (demonstrated by decreased percent of androgen receptor nuclear localization [%ARNL] and increased microtubule bundling) as shown by CTC analysis.

Thirty-five patients (55.6%) achieved at least a 50% PSA response vs the 45.5% historical rate.

Thirty-three patients (54.1%) achieved at least a 30% PSA decline by C4 and did not switch taxane, 15 patients (24.6%) did not see at least a 30% PSA decline and switched taxanes.

Of the patients that switched, 7 patients (46.7%) achieved a PSA response exceeding 50%.

RELATED: PSA Density More Accurate Than PSA for Predicting Prostate Cancer

In the patients who were CTC-evaluable, decreases in %ARNL were associated with a higher rate of at least a 50% PSA decrease (P = .009).

While both primary endpoints were reached, the study authors noted that these results are not sufficient for changing the standard of care in patients with mCRPC. Further study is warranted.

Reference

  1. Antonarakis ES, Tagawa ST, Galletti G, et al. 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. J Clin Oncol. 2017 Jun 20. doi: 10.1200/JCO.2017.72.4138 [Epub ahead of print]

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