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benefit would not be worthwhile. Assuming an MSI
prevalence of 5% and an increase in response rate for
MSI-positive patients on immunotherapy from 2% to 40%,
the full population response rate would only be improved
by (0.40 0.02) 0.05 = 1.9%. We believe that a more
meaningful demonstration of clinical utility is offered by
our recent study that suggested that PSA50 response rates
were higher in patients whose AR-V7 results were used to
change clinical decisions compared to those for whom the
test did not change management .
Lastly, the authors touched on the topic of the ability to
identify non-responders, using failure to achieve PSA50 as a
measure of non-response. Again, this calculation is heavily
influenced by how we define clinical response Despite
favorable PSA changes in a subset of men, it must still be
remembered that PSA progression–free survival and radio-
graphic progression–free survival estimates among AR-V7+
patients receiving first-line abi/enzawere only3mo and 4mo,
respectively.Whilewe agree that there is a need for predictive
markers that are more specific in identifying non-responders
(ie, with a highnegative predictive value), it is unreasonable to
expect a biomarker to detect a high proportion of non-
responders if PSA50 is used as the only measure of ‘‘response’’
in the first-line CRPC setting. Moreover, the AR-V7 test has
recently been analytically validated in a Clinical Laboratory
Improvement Amendments laboratory , and its negative
prognostic value was confirmed in the ARMOR3-SV trial
testing enza versus galeterone Overall, accumulating data
support the poor prognosis of AR-V7+ patients and the
importance of developing novel agents to treat AR-V7+ CRPC
. From that perspective, we believe that the authors will
agree with us on the utility of AR-V7 testing in biomarker-
driven trials and in the development of novel agents with
activity in this setting.
Conflicts of interest: Jun Luo has served as a paid consultant/advisor for
Astellas, has been a speaker for Sanofi and Gilead, has received research
funding from Sanofi and Mirati, and is co-inventor of a technology that
has been licensed to Tokai. Emmanuel S. Antonarakis has served as a paid
consultant/advisor for Janssen, Astellas, Sanofi, Dendreon, Essa, and
Medivation; has received research funding from Janssen, Johnson &
Johnson, Sanofi, Dendreon, Exelixis, Genentech, Novartis, and Tokai; and
is co-inventor of a technology that has been licensed to Tokai. Brandon
Luber and Hao Wang have nothing to disclose.
References
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[2] Li H, Wang Z, Tang K, et al. Prognostic value of androgen receptor
splice variant 7 in the treatment of castration-resistant prostate
cancer with next generation androgen receptor signal inhibition: a
systematic review and meta-analysis. Eur Urol Focus. In press.
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Jun Luoa,*
Brandon Luberb
Hao Wangb
Emmanuel S. Antonarakisb
aDepartment of Urology, The James Buchanan Brady Urological Institute,
Johns Hopkins University School of Medicine, Baltimore, MD, USA
bDepartment of Oncology, Johns Hopkins University School of Medicine,
Baltimore, MD, USA
*Corresponding author. Department of Urology, The James Buchanan
Brady Urological Institute, Johns Hopkins University School of Medicine,
600 N Wolfe Street, Baltimore, MD 21287, USA. Tel. +1 443 2875625.
E-mail address: (J. Luo).
June 21, 2017
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