©TheCanadian Journal ofUrology™: International Supplement, April 2014
In thedegarelixgroups,medianLHandFSH levels
decreased rapidly and remained suppresseduntil the
end of the study, whereas as expected LH and FSH
levels showed an initial increase for patients in the
leuprolidegroup,andFSH levelsdidnotfalltothesame
extent as they did in the degarelix arms. In parallel
with the testosterone results, the data for prostate-
specific antigen (PSA) reduction showed a statistical
differenceat7,14,and28days,withsignificantlygreater
suppression than in the leuprolide group, and this
findingcorrelatedwithasignificantly lowerriskofPSA
failureordeath. Howeverby1yearoverallsurvivaldid
notdiffersignificantlybetweenthedegarelix240/80mg
group and the leuprolide group (probability of death
at 1 year, 2.6% versus 4.9%, respectively, NS). On the
basisofthesefindings, theU.S.FDAapproveddegarelix
injectiononDecember24,2008asatreatmentofpatients
withadvancedprostate cancer.
When the trial was extended beyond 1 year, the
higher percentage of patients on degarelix versus
leuprolidehaving aPSAof < 4persistedout to about
73weeks, Figure 2. It is important to note, however,
that thepatientson leuprolidewereallowed toswitch
todegarelixafter52weeks,withtheresultthatbetween
weeks 52 and 73, the curve for progression-free
survival inpatientson leuprolideconvergedwith that
forpatientsondegarelix. Therefore, by theendof the
followupperiod theprogression-free survival results
wereessentiallyequivalent in the twoarms, Figure3.
This prostate-specific antigen (PSA) progression-
free survival comparison remains very controversial
especially in light that the primary endpoint of Tnon-
Figure 3.
In the long term follow up extension study of the pivotal Klotz et al phase III RCT, the patients in
the leuprolide arm could be switched todegarelix at the 1 year point (marked by the vertical dotted line). This
switch from leuprolide todegarelix resulted in the survival curves convergingat approximately3year followup.
Crawford et al suggest in thepeer reviewedpublicationof thisdata that this implies that degarelixmaybemore
effective than leuprolide. While intriguing andhypothesis-generating, thiswas not a pre-planned analysis and
it remains speculative if degarelix is trulymore effective than a comparable LH-RH agonist based on this data.
7
Reprintedwithpermission.
24
Utilityof LHRH antagonists for advancedprostate cancer
