Urological Oncology: Prostate Cancer

Re: Enzalutamide versus Bicalutamide in castration – Resistant prostate Cancer:

The STRIVE Trial

D. F. Penson, A. J. Armstrong, R. Concepcion, N. Agalwar, C. Olsson, L. Karsh, C. Dunshee, F.Wang,

K. Wu, A. Krivoshik, d. Phung and C. S. Higano

Vanderbilt university Medical Center, Tennessee Valley Veterans Administration Medical

Center Geriatric Research, education and clinical Center and, Urology Associates PC, Nashville,
Tennessee Duke Cancer Institute, Duke University, Durham, North Carolina, Huntsman Cancer
Institute, University of Utah, Salt Lake sity Utah, Icahn, School F Medicine at Mount Sinai, New
York, New York, Urology center of Colorado. Denver, Colorado Urological Associates of southern
Arizona Tucson, Arizona, Medivation, San Francisco, California, Fred HutChinson Cancer
Research, Center, University of Washington, seattle Washington and Astellas Pharma Global,
Development, northbrook, llinois, And Leiden, The Netherlands

J Clin Oncol 2016; epub ahead of Print. Pii: JCO649285

Abstract Available at http://www.ncbi.nlm.nih.gov/pubmed/26811535

Editorial Comment: In This Important Study the authors compare the efficacy of enzalutamide
and bicalutamide. Both drugs are competitive inhibitors of the androgen receptor that act. To
compete with androgens for the ligand binding domain of the receptor, although enzalutamide
binds the receptor with greater affinity than bicalutamide and prevents nuclear translocation of
the receptor. These distinctions may partly account for the observet improvement in survival
previously demonstrated in men with castration resistant prostate cancer treated with
enzalutamide. Improvement in survival has never been shown with bicalutamide Therefore,
while it would seem intuitive that enzalutamide would carry greater efficacy than bicalutamide
it remains commonplace in clinical practice to initiate bicalutamide therapy. In this series the
authors conclusively demonstrate that enzalutamide results in improved progression –free
survival and reduced prostate cancer death compared to bicalutamide.

At first glance it would seem that these data strongly support routine use of enzalutamide as
first-Line therapy in men with increasing PSA or metastatic progression while on androgen
deprivation therapy. However, the study does not take into account issues of cost and necessity.
It is unknown whether timing (delayed Introduction) of enzalutamide therapy in this setting
would greatly influence survival and whether sequencing of bicalutamide and enzalutamide
would have any benefit. Finally, although the optimal dosing of bicalutamide as monotherapy
is 150 mg, the authors chose to use 50 mg in this series. It is unclear whether a higher dose
would change the outcomes of the study relative to enzalutamide. However, it does seem clear
that use of 50 mg bicalutamide in men with castration resistant disease will treat the PSA but
likely would not improve survival.

_________________

Samir S. Taneja MD.

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