EURURO Vol. 72 No. 6

Letter to the Editor

Re: Emmanuel S. Antonarakis, Changxue Lu, Brandon

Luber, 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;35:2149–56

AR-V7 Testing: What’s in it for the Patient?

We congratulate Antonarakis et al

[1]

on their study and for

providing additional important data on AR-V7 in the setting

of castration-resistant prostate cancer (CRPC). By expanding

on their prior work, the authors confirm the negative

prognostic impact of circulating tumor cell (CTC) detection

and CTC-based AR-V7 mRNA detection in patients with

CRPC. The authors state that assessing these biomarkers

may be useful in predicting responses to therapies. On the

basis of their data, they propose a shift from current clinical

practice towards biomarker-based treatment decisions

( Fig. 1

A). We find the study data in the first-line setting

noteworthy for several reasons.

First, by showing that four of 15 CTC

AR-V7

patients

(26%) achieved prostate-specific antigen decreases to

50%

from baseline, the authors resolve a prior controversy

regarding these unexpected responses to abiraterone or

enzalutamide

[2–4]

. We previously reported a 20% response

rate among CTC

AR-V7

patients on abiraterone or

enzalutamide

[3]

. Antonarakis et al

[1]

used appropriate

clinical trial criteria to confirm these unexpected responses.

Thus, the AR-V7 status in CTCs cannot entirely predict non-

response, and CTC

AR-V7

patients should not be

systematically denied abiraterone or enzalutamide treat-

ment

[3] ,

especially given the response rates to alternative

treatment options

[5] .

Second, a major as-yet unanswered question that must

be addressed before a biomarker can be translated to the

clinic is the ability of CTC AR-V7 testing to predict responses

or non-responses to treatment. Importantly, prospective

biomarker-stratified trials are currently missing. In their

study, Antonarakis et al

[1]

did not use biomarker-based

treatment stratification of patients, and all patients enrolled

received abiraterone or enzalutamide on the basis of a

clinical decision. The data thereby allow assessment of

overall response rates in current clinical practice

( Fig. 1 B

The overall response rate to abiraterone or enzalutamide in

the first-line setting was 66.9% (

= 83 responders from

124 patients). These data allow estimation of the overall

benefit from implementation of CTC AR-V7 testing and

treatment stratification in the first-line setting. As pointed

out in several publications

[5–7]

, the key therapeutic

alternative for patients when identified as CTC

AR-V7

taxane-based chemotherapy, whereas treatment decisions

for other subgroups remain the same. To estimate the

response rates to chemotherapy in the specific subgroup of

AR-V7

patients, we used recent meta-review data that

showed a response rate of 35.8% (

= 19/53)

[8]

. Compari-

son of these response rates in the AR-V7

setting between

abiraterone or enzalutamide (26.6%;

= 4/15) and taxane-

based chemotherapy (35.8%;

= 19/53) did not reveal a

significant difference (

= 0.76, Fisher’s exact test). When

applying the 35.8% response rate to taxanes to the 15 AR-

patients in the Antonarakis et al study

[1] ,

we calculated

the theoretical number of responders as 5.37 patients

E U R O P E A N U R O L O G Y 7 2 ( 2 0 1 7 ) e 1 6 8 – e 1 6 9

available at

www.scienced irect.com

journal homepage:

www.europeanurology.com

[(Fig._1)TD$FIG]

Fig. 1 – AR-V7 testing: what’s in it for the patient? (A) Currently, no

predictive biomarker has been established in castration-resistant

prostate cancer. (B) Based on the data reported by Antonarakis et al

[1] ,

the diagram depicts the estimated overall benefit from biomarker-

based patient stratification. The asterisk * indicates the predicted

number of CTC

AR-V7

responders to taxane-based chemotherapy on

the basis of recent meta-review data

[8] .

Note that prospective

biomarker-stratified trial data are currently missing. CTC = circulating

tumor cell.

http://dx.doi.org/10.1016/j.eururo.2017.06.031

0302-2838/