E169 1030
(rounded up to 6 patients). Since treatment in CTC and AR-
V7 patients would not change, comparison of current
clinical practice and biomarker-stratified treatment deci-
sions shows two additional AR-V7
+
responders, resulting in
an overall response rate of 68.5% (
n
= 85 responders from
124 patients;
Fig. 1 B). Thus, the overall benefit from
universal AR-V7 testing can be estimated at approximately
+1.5% in the first-line setting. Clearly these estimates differ
from prior studies
[9], are theoretical, and require
prospective clinical trials for confirmation. However, such
approximations are—in our opinion—critical for effect size
predictions, trial design, and assessment of the overall
clinical significance of a predictive biomarker.
Third, by specifying the number of non-responders in all
three proposed subgroups, the study clearly shows that the
AR-V7
+
[6_TD$DIFF]
subgroup contains only 27% of all non-responders
(
n
= 11 AR-V7
+
non-responders among a total of 41 non-
responders). In other words, a striking 61% of all non-
responders (
n
= 25/41) belong to the CTC
+
AR-V7 sub-
group. Therefore, these important new data clearly outline
our inability to effectively predict non-responses for a
majority of patients and thus the need for additional
predictive biomarkers.
Conflicts of interest:
Julie Steinestel, Christof Bernemann, and Andres J.
Schrader have received honoraria, consulting fees, or travel support from
Janssen, Astellas, Sanofi, Novartis, and Pfizer. Christof Bernemann has
received research funding from Janssen. Jochen K. Lennerz has nothing to
disclose.
References
[1]
Antonarakis ES, Lu C,[9_TD$DIFF]
Luber B, et al. Clinical significance of androgen receptor splice variant-7 mRNA detection in circulating tumor cells of men with metastatic castration-resistant prostate cancer treated with first- and second-line abiraterone and enzalutamide. J Clin Oncol 2017;[10_TD$DIFF]
35:2149–56.[2]
Antonarakis ES, Scher HI. Do patients with AR-V7-positive prostate cancer benefit from novel hormonal therapies? It all depends on definitions. Eur Urol 2017;71:4–6.[3]
Bernemann C, Schnoeller TJ, Luedeke M, et al. Expression of AR-V7 in circulating tumour cells does not preclude response to next genera- tion androgen deprivation therapy in patients with castration resis- tant prostate cancer. Eur Urol 2017;71:1–3.
[4]
Steinestel J, Bernemann C, Schrader AJ, Lennerz JK. Reply from authors re: Emmanuel S. Antonarakis, Howard I. Scher. Do patients with AR-V7-positive prostate cancer benefit from novel hormonal therapies? It all depends on definitions. Eur Urol 2017;71:4–6, Unsplicing a conflict. Eur Urol 2017;71:6–7.[5]
Antonarakis ES, Lu C, Luber B, et al. Androgen receptor splice variant 7 and efficacy of taxane chemotherapy in patients with metastatic castration-resistant prostate cancer. JAMA Oncol 2015;1:582–91.[6]
Antonarakis ES, Lu C, Wang H, et al. AR-V7 and resistance to enza- lutamide and abiraterone in prostate cancer. N Engl J Med 2014;371:1028–38.[7]
Handy CE, Antonarakis ES. Sequencing treatment for castration- resistant prostate cancer. Curr Treat Options Oncol 2016;17:64.[8] Li H, Wang Z, Tang K, et al. Prognostic value of androgen receptor
splice variant 7 in the treatment of castration-resistant prostate
cancer with next generation androgen receptor signal inhibition:
a systematic review and meta-analysis. Eur Urol Focus. In press.
https://doi.org/10.1016/j.euf.2017.01.004 .[9] Steinestel J, Luedeke M, Arndt A, et al. Detecting predictive androgen
receptor modifications in circulating prostate cancer cells. Oncotar-
get. In press.
http://dx.doi.org/10.18632/oncotarget.3925 .Julie Steinestel
a
[5_TD$DIFF]
y
,
*
Christof Bernemann
a,
y
Andres J. Schrader
a
Jochen K. Lennerz
b
a
Department of Urology, University Hospital Muenster,
Muenster, Germany
b
Department of Pathology, Center for Integrated Diagnostics,
Massachusetts General Hospital/Harvard Medical School,
Boston, MA, USA
*Corresponding author. Department of Urology, University Hospital
Muenster, Albert-Schweitzer Campus 1, 48149 Muenster, Germany.
Tel. +49 251 8347442; Fax: +49 251 8349739.
E-mail address:
julie.steinestel@ukmuenster.de(J. Steinestel).
y
These authors contributed equally to this work.
June 21, 2017
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