EURURO Vol. 71 No. 5

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They have linked AR-V7 status to progression-free and overall
survival in 36 patients with castration-resistant prostate
cancer undergoing treatment with abiraterone or enzaluta-
mide. They report that median progression-free and
overall survival in AR-V7–negative patients exceeded that
in AR-V7–positive patients by more than 1 yr. They conclude
that the presence of AR-V7 may predict resistance to
hormonal therapy.
Expert’s comments:
Biomarker-guided selection of the most suitable treatment
has become an important trend in oncology in general [2] and
in urology [3]. A role for AR-V7 in responsiveness to antihor-
monal therapy has been proposed before [1]. The main value
of the study by del Re et al is establishing a method for AR-V7
quantification based on mRNA circulating in plasma. This is
apparently more sensitive than assessing circulating tumor
cells, as it has fewer false negatives. Moreover, in contrast to
tumor biopsies, it allows serial measurements to account for
possible shifts in tumor genotype and phenotype over time.
Del Re et al claim that their plasma-based test predicts
survival, but what they have shown is association rather
than predictivity. Convincing proof of predictive value
(compared to association) requires prospective studies,
preferentially in two independent cohorts. While primarily
developed for commercial drug development, guidance by
the US Food and Drug Administration on the development
of biomarkers in oncology may also benefit academic
investigators [2]. For optimal treatment results, the quality
of biomarker validation should not differ between academic
and commercial investigators.
Demonstrating that AR-V7 status is associated with
length of survival at the group level does not necessarily
help the treatment decision for an individual patient. Future
prospective studies are required to determine whether AR-
V7–guided treatment has better outcomes than treatment
allocation without biomarkers. It has been argued that such
studies are sparse because they are very expensive [4]. The
method developed by del Re et al may make it easier and
less costly to perform such trials. Therefore, the ultimate
value may reside in developing a technology that allows
prospective outcome trials with limited patient numbers
and budget.
Conflicts of interest: The author has been a consultant for Boehringer
Ingelheim, Dr. Wilmar Schwabe, Sanofi, and Velicept Therapeutics, is a
shareholder in Velicept Therapeutics, and was an employee of
Boehringer Ingelheim (2011–2016).
References
[1]
.
[2]
[3]
.
[4]
.
Martin C. Michel*
Pharmacology Department, Johannes Gutenberg University, Mainz,
Germany
*Pharmacology Department, Johannes Gutenberg University, Obere
Zahlbacher Strasse 67, Mainz 55131, Germany.
E-mail address:
# 2017 European Association of Urology.
Published by Elsevier B.V. All rights reserved.
Re: Adjuvant Sunitinib in High-risk Renal-cell
Carcinoma after Nephrectomy
Ravaud A, Motzer RJ, Pandha HS, et al
N Engl J Med 2016;375:2246–54
Expert’s summary:
In this phase 3 trial (S-TRAC, NCT00375674), 1 yr of adjuvant
sunitinib was compared with placebo in patients who under-
went full surgical resection of high-risk clear cell renal-cell
carcinoma (RCC). Sunitinib was administered orally at a dose
of 50 mg/d in the classic 4-wk on/2-wk off schedule. The
primary endpoint was disease-free survival, which was sig-
nificantly prolonged in the sunitinib arm (hazard ratio: 0.76,
95% confidence interval: 0.59–0.98, p = 0.03). There were no
differences in overall survival (hazard ratio: 1.01, 95% confi-
dence interval: 0.72–1.44, p = 0.94). The incidence of Grade
3 and 4 adverse events was 48% in the sunitinib arm and 12%
in the placebo arm. Forty-six percent of patients in the suni-
tinib arm had dose reductions, of which > 90% were due to
adverse events [1].
Expert’s comments:
More than 50% of patients with high-risk RCC will recur
following complete surgical resection [2], which is likely due
to growth of microscopic metastases that are present at the
time of diagnosis or which develop during the perioperative
period. The aim of an adjuvant therapy is to eradicate these
microscopic metastases, and ultimately improve disease-free
and overall survival. Several adjuvant trials have been initiated
to eradicate these possible microscopic tumour deposits, in-
cluding trials with sunitinib, sorafenib, pazopanib, and axitinib.
These therapies have been the standard of care in the palliative
setting for about a decade; however, complete tumour eradi-
cation of visible metastases has rarely been reported.
The present study showed that the risk for disease
recurrence is reduced by 24% with adjuvant sunitinib, with a
5-yr disease-free survival rate of 59% in the sunitinib arm,
and 51% in the placebo arm. This difference in disease-free
survival developed within the 1st yr and remained relatively
stable thereafter. Thus, it appears that sunitinib discontinu-
ation after 1 yr does not lead to rebound growth of
microscopic metastases due to revascularisation. Patients
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