©TheCanadian Journal ofUrology™: International Supplement, April 2014
and 21.7months for patients whowere treatedwith
placebo (p=0.03), asurvival advantageof 4.1months
while possessing a relatively benign safety profile.
The IMPACT study randomizedpatients 2:1 toactive
treatment versus placebo. Patients who progressed
on theplacebo armhad theoptionof participating in
a companion studywhere they couldbe treatedwith
a reactivated frozenproduct (APC8015F). Asurvival
advantagewas apparent despite the highpercentage
of subjects (75.6%) randomly assigned to APC-
placebowho, followingobjectivediseaseprogression,
subsequently received the frozenproduct. APC8015F
wasa formulationsimilar tosipuleucel-Tconsistingof
APCs prepared from cryopreservedAPC and loaded
with PAPGM-CSF. Adverse events seenmore often
insipuleucel-T treatedpatients than in thosereceiving
placebo included predominantly chills, fatigue, and
pyrexia that were Grade 1 or 2 in severity and of
short duration (1 or 2 days), resulting in minimal
discontinuationof treatment (< 2%), seeTable 1.
A highly controversial report using previously
unpublished IMPACT trial data has suggested that
the increased overall survival in sipuleucel-T-treated
men could be an artifact. The authors speculated
TABLE 1.
Common adverse events reported in the IMPACT trial (25%or greater incidence)
4
Event
Sipuleucel-T (n=338)
Placebo (n=168)
AllGrades
Grade 3-5
AllGrades
Grade 3-5
n (%)
n (%)
n (%)
n (%)
Any
334 (98.8)
107 (31.7)
162 (96.4)
59 (35.1)
Chills
183 (54.1)
4 (1.2)
21 (12.5)
0
Fatigue
132 (39.1)
4 (1.2)
64 (38.1)
3 (1.8)
Backpain
116 (34.3)
12 (3.6)
61 (36.3)
8 (4.8)
Pyrexia
99 (29.3)
1 (0.3)
23 (13.7)
3 (1.8)
Nausea
95 (28.1)
2 (0.6)
35 (20.8)
0
TABLE 2.
PSAquartile data from the IMPACT studydemonstrating improved survivalwith lower baseline
PSA levels
35
BaselinePSA (ng/mL), n= 128
≤ 22.1
> 22.1-50.1
> 50.1-134.1
> 134.1
MedianOS (months)
Sipuleucel-T
41.3
27.1
20.4
18.4
Control
28.3
20.1
15.0
15.6
Difference
13.0
7.1
5.4
2.8
Hazard ratio
0.51
0.74
0.81
0.84
(95%CI)
(0.31, 0.85)
(0.47, 1.17)
(0.52, 1.24)
(0.55, 1.29)
due to age-related differences in the placebo group
(more oldermen in the placebo group) had a higher
chance of dying, because removing white cells was
harmful.
31
These highly controversial findings have
beendefinitively refutedby several other authors.
32,33
As noted, the majority of patients on the placebo
arm of the IMPACT study received salvage therapy
upon progressionwith the frozen product. We have
previouslyreportedonananalysisofpost-progression
treatmentwithAPC8015F. This trial designmayhave
actually prolonged survival of subjects in the control
armofsipuleucel-tphaseIIItrialspotentiallydecreasing
the absolute overall survival benefit seen with the
treatment.
34
This secondary analysis suggested the
absolutesurvivaladvantageofsipuleucel-Tmaybeup
to 10.9months andpossibly longerwhen the effect of
thesalvage therapywasconsidered in theplaceboarm.
TheuseofPSAinthesettingofsipuleucel-Trequires
someclarification. PSAresponsesmaynotbeobserved
inpatientswhohave favorableoverall survivalbenefit
form sipuleucel-T. In an exploratory analysis of the
IMPACT trial, the greatest magnitude of benefit with
sipuleucel-T treatmentwasseen inpatientswithbetter
baselineprognosticfactors,and inparticularthosewith
52
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