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Adjuvant sunitinib increases disease-free survival in patients
with high-risk RCC after nephrectomy
T
he S-TRAC trial reported by Ravaud
and colleagues is a phase 3 trial of the
VEGF pathway inhibitor sunitinib
for adjuvant treatment of high-risk renal
cell carcinoma after nephrectomy. It is
one of the first studies demonstrating the
benefit of adjuvant therapy in patients
with renal cell carcinoma. Although one
should be cautious when interpreting the
results, the investigators have allowed
for an optimistic view when managing
the disease in the higher risk patient
population, where recurrence rates after
nephrectomy are approximately 50%.
A total of 615 patients with high-risk
clear cell renal cell carcinoma following
nephrectomy were randomised to either
placebo or full dose 50 mg of sunitinib for
4 weeks on, 2 weeks off for 1 year or until
disease recurrence. Patients with suspected
metastases were excluded from the study.
The primary endpoint was met with a
significantly longer disease-free survival
of 6.8 years with sunitinib compared with
5.6 years with placebo. At 5 years, 59.3%
were disease-free in the sunitinib group
versus 51.3% in the placebo group. Overall
survival data was not complete.
Adverse events were responsible for dose
reductions in 34.3% of the sunitinib
group compared with only 2% of placebo
patients. There were more treatment
interruptions (46.4% vs 13.2%) as well as
more treatment discontinuations (28.1%
vs 5.6%) in the sunitinib group. Despite a
similar number of serious adverse events,
there were significantly more frequent
grade 3 adverse events in the sunitinib
arm (48.4% vs 12.1%).
This is a positive trial promoting the
use of adjuvant therapy. However, it is
important to highlight that more than 50%
of the patients in the placebo arm did not
experience any recurrence. Furthermore,
similar studies, including the ASSURE
trial, have demonstrated no differences in
disease free or overall survival in a similar
setting. A number of comparable trials
are underway and where there currently
remains equipoise in outcomes and
opinion, the future will tip the scales one
way or another.
Adjuvant sunitinib in high-risk
renal-cell carcinoma after
nephrectomy
N Engl J Med
2016;375:2246-2254. A Ravaud, RJ
Motzer, HS Pandha, et al; S-TRAC Investigators
Take-home message
•
This double-blind, phase 3 trial included 615
patients with locoregional, high-risk clear cell
renal cell carcinoma who were randomised to
receive sunitinib or placebo. Patients receiving
sunitinib exhibited a significantly longer
median disease-free survival compared with
patients receiving placebo (6.8 vs 5.6 years;
P = 0.03). Dose reductions, interruptions, and
discontinuations were more frequent in patients
receiving sunitinib. The occurrence of serious
adverse events was similar between the groups,
with no deaths attributed to treatment.
•
The study results showed that sunitinib
significantly lengthened disease-free survival
in patients with locoregional clear cell RCC
at high risk for tumour recurrence following
nephrectomy, although this benefit was
accompanied by increased adverse events.
10-year outcomes after monitoring,
surgery, or radiotherapy for
localized prostate cancer
N Engl J Med
2016;375:1415-1424. FC Hamdy,
JL Donovan, JA Lane, et al; ProtecT Study Group.
Take-home message
•
This was a multicentre, randomised trial
including 1643 men with newly diagnosed
localised prostate cancer, which was designed
to compare three potential treatment strategies:
active monitoring, radical prostatectomy, and
external-beam radiotherapy. At a median follow-
up of 10 years, there were only 17 prostate
cancer-specific deaths in the three treatment
groups combined (prostate cancer-specific
survival of at least 98.8% in all groups at 10
years). There was no significant difference in
overall survival among the patients whether
treated with observation, prostatectomy, or
external-beam radiotherapy. Metastatic disease
was also rare irrespective of treatment arm (62
of 1643 patients) but was more common in
the observation arm compared with either the
upfront radiation or surgery arms (33 vs 13 vs 16
events for observation, surgery, and radiation
groups, respectively).
•
The authors concluded that, while prostate
cancer-specific mortality rates remained low
despite the treatment strategy employed, surgery
and radiotherapy resulted in lower incidences of
disease progression and metastases.
Positive 10-year outcomes for localised prostate cancer across
treatment strategies
T
he ProtecT trial is a highly
commendable effort evaluating
10-year outcomes following active
monitoring, surgery or radiotherapy for
localised PSA-detected prostate cancer.
Many authors have failed to recruit
to similar studies in the past. Both
oncological and functional outcomes
of patients were evaluated. A total of
545 patients were randomised to active
monitoring, 553 to radical prostatectomy
and 545 to radiotherapy. At a median
follow-up of 10 years, there were no
significant differences in prostate cancer-
specific or overall survival between groups.
Of note, there was a notable increase in
disease progression and metastasis in men
managed with active monitoring. With
respect to functional outcomes, worse
urinary continence and erectile function
was observed following surgery, whereas
voiding and bowel-related symptoms were
worse after radiotherapy.
There are a number of caveats one
must consider when evaluating the data
presented. The ProtecT authors assumed
a prostate cancer mortality of 15% when
powering the study. As the trial progressed,
this figure was however significantly
lower at 1%. Although the result is huge,
conclusions are drawn from very few
events (17 deaths).
It is important to recognise that modern
day active surveillance regimens
incorporate serial PSA testing, digital
rectal examination, serial prostate biopsies
or imaging. The trial protocol mandated
only rectal examination and PSA testing.
While the conclusions do allow for
additional support using conservative
management for select patients, however,
one must not confuse modern day active
surveillance and active monitoring used in
the trial design.
The vast majority of patients in the
trial exhibited low-risk disease; many of
these patients would be considered for
modern day active surveillance. Today,
active treatment would be reserved for
intermediate and higher risk prostate
cancer. It is important to note that although
radical treatment is effective in reducing
disease progression and metastases,
based on the data presented, this did not
translate into improved survival.
EDITOR’S PICKS
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VOL. 2 • NO. 1 • 2017