Highlights
- •Docetaxel (D) and enzalutamide (E) have different mechanism of action.
- •They are efficacious in metastatic castration-resistant prostate cancer (mCRPC).
- •We compared their combination versus docetaxel alone in first-line mCRPC.
- •This combination increased the 6-month disease control rate by 15.3%.
- •We observed more grade III- toxicities in DE arm than in D arm.
Abstract
Background
Pre-clinical data suggest that docetaxel and enzalutamide interfere with androgen
receptor translocation and signalling. The aim of this study is to assess the efficacy
of their concurrent administration in the first-line treatment for metastatic castration-resistant
prostate cancer (mCRPC).
Methods
In this open-label, randomised, phase II trial, previously untreated mCRPC patients
were randomised 1:1 to receive eight 21-d courses of docetaxel 75 mg/m2, oral prednisone 5 mg twice daily and oral enzalutamide 160 mg/d (arm DE), or the
same treatment without enzalutamide (arm D). The primary end-point was the percentage
of patients without investigator-assessed disease progression 6 months after the first
docetaxel administration.
Results
The 246 eligible patients were randomly assigned to receive docetaxel, prednisone
and enzalutamide (n = 120) or docetaxel and prednisone (n = 126). The 6-month progression rate was 12.5% (95% confidence interval [CI] 8.1–20.6)
in arm DE and 27.8% (95% CI 22.8–39.4) in arm D (chi-squared test 10.01; P = 0.002). The most frequent grade III–IV adverse events were fatigue (12.5% in arm
DE versus 5.6% in arm D), febrile neutropenia (9.3% versus 4.0%) and neutropenia (7.6%
versus 5.6%).
Conclusions
The combination of enzalutamide and docetaxel appears to be more clinically beneficial
than docetaxel alone in previously untreated mCRPC patients, although serious adverse
events were more frequent. Our findings suggest that first-line treatment with this
combination could lead to an additional clinical benefit when prompt and prolonged
disease control is simultaneously required. Clearly, these results should be considered
cautiously because of the study’s phase II design and the absence of an overall survival
benefit.
Trial registration numbers
EudraCT 2014-000175-43 – NCT02453009.
Graphical abstract
Graphical Abstract
Keywords
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Article info
Publication history
Published online: August 03, 2021
Accepted:
June 6,
2021
Received in revised form:
May 22,
2021
Received:
April 21,
2021
Identification
Copyright
© 2021 Elsevier Ltd. All rights reserved.
