©TheCanadian Journal ofUrology™: International Supplement, April 2014
5
GomellaETAL.
notethesuperiorityofthe latter indelayingSRE.
23,29
The
roleofbone targeted therapysuchasradium223 in the
settingofmCRPC isalsoaddressed in thissupplement
byDenandassociates.
24
SequencingmCRPC: an evolving challenge
The availability of numerous agents in the CRPC
space iscertainlygoodnews. However, thedownside
of having multiple choices across the spectrum of
advanceddisease creates uncertainty concerning the
optimumway tocombineorsequence themedications
toderivemaximumbenefit. Dr.Dreicer thoughtfully
considers where some of these newer agents might
be best positioned in a “clinically rational and
economicallyviablemanner”.
31
Henotes that certain
sequencing issues will be addressed by formal trials
suchasanongoingphase III trialrandomizingpatients
withmCRPC toreceiveeitherdocetaxelorcabazitaxel
(
).
What’snext in advancedprostate cancer?
Dozens of clinical trials evaluating new therapeutics
inmenwithmetastaticprostatecancerare inprogress.
Some of these include newfirst inman agentswhile
others involve theapplicationofexistingagents innew
settings or in combinationwith other agents. While
manyagentsunderevaluationsuchasARN-509,TAK-
700andTOK-001continueon the themeof interacting
within the androgen axiswhile others interferewith
other pathways of prostate cancer progression such
as cabozantinib and OGX-011. Based on the proof
of principle that of sipuleucel-T immunotherapy is
effective, this area continues to be a targeted area of
interest inprostate cancerwith several other prostate
cancervaccinesand immunecheckpoint inhibitors in
latestageclinical trials. Thoresonandassociateshave
reviewed theemerging therapies inCRPCandfocuson
someof the trials thatwillprovidenear term results.
32
Conclusions
The rapid advances in our therapeutic options for
advancedprostatecancerareimpressiveandatthesame
time overwhelming and sometimes difficult to place
in proper clinical context. Table 2 summarizes some
of the recent agents, trials, and outcomes of the latest
medicationsused in themanagementofmCRPC. One
challengegoing forward is todemonstrate thatsomeof
theseneweragents indevelopment are superior to the
previously approved agents. Since patients who fail
someof theseneweragentscanbe treatedwithexisting
drugs iftheyprogress, theeffectivenessofthenewdrug
maynot beaspronounced.
Prostate cancer guidelines frommanyorganizations
suchastheAUA,EAU,CUAandNCCNhaveincorporated
most of these new therapeutic agents and approaches
to advanced and CRPC.
23,30,39,40
As clinicians begin to
understand therationale for theseneweragentsand the
practicalaspectsoftheirclinicalapplicationtheirusewill
likelyexpand tobenefitmoreeligiblepatients.
TABLE 2.
Agentswithoverall survival benefit inmetastatic castration resistant prostate cancer
Drug
Trial
Comparator
Primaryendpoint
FDA
approval
Chemotherapy-naïve
Abirateroneacetate+prednisone COU-AA-302
33
Placebo+prednisone
OSbenefit 5.2months* Dec2012
Sipuleucel-T
IMPACT
16
Placebo
OSbenefit 4.1months Apr 2010
Radium223dichloride
ALSYMPCA
34
Placebo
OSbenefit 3.6months May2013
Enzalutamide (interimanalysis) PREVAIL
20
Placebo
OSbenefit 2.2months N/A
Post-chemotherapy
Abirateroneacetate+prednisone COU-AA-301
35
Placebo+prednisone
OSbenefit 4.6months Apr 2011
Enzalutamide
AFFIRM
36
Placebo
OSbenefit 4.8months Aug2012
Cabazitaxel +prednisone
TROPIC
37
Mitoxantrone+prednisone OSbenefit 2.4months June2010
Docetaxel +prednisone
TAX327
38
Mitoxantrone+prednisone OSbenefit 2.4months May2004
FDA=Food andDrugAdministration;OS=overall survival
*p = 0.0151. Did not meet the prespecified value for statistical significance (Pre-specified significance by O’Brien-Fleming
boundary= 0.0008)
