Annual Meeting Proceedings Part 1 - American Society of Clinical ...

324s Genitourinary Cancer
TPS4690 General Poster Session (Board #16A), Sun, 8:00 AM-12:00 PM
What is optimal timing of post prostatectomy radiotherapy? Is adjuvant
radiotherapy equivalent to early salvage radiotherapy? The “RAVES” phase
III randomized clinical trial. Presenting Author: Maria Pearse, Auckland
City Hospital, Auckland, New Zealand
Background: Three randomised trials have demonstrated a significant
benefit of adjuvant post prostatectomy radiotherapy in patients with
positive margins, extra capsular extension or seminal vesicle involvement,
and it should be regarded as current standard of care. However, adopting
this approach will expose nearly half of such patients to unnecessary
radiotherapy and potential treatment morbidity. Salvage radiotherapy, if
given early, is recognised to be effective. The RAVES trial is designed to
compare these two approaches, and was developed in collaboration with
the Trans Tasman Radiation Oncology Group (TROG), Australian and New
Zealand Urogenital and Prostate Trials Group (ANZUP) and the Urological
Society of Australia and New Zealand (USANZ). It aims to test the
hypothesis that active surveillance with early salvage radiotherapy is
non-inferior to adjuvant radiotherapy with respect to risk of biochemical
failure (defined as PSA level � 0.40 ng/mL and rising). Methods: Patients
must have at least one of the following risk factors: positive margins,
extracapsular extension or seminal vesicle involvement. They must start
radiotherapy within 4 months of radical prostatectomy (RP) and have an
undetectable PSA (� 0.10 ng/ml) prior to randomisation. Patients receiving
androgen deprivation or who have an artificial hip are excluded. Eligible
patients are randomised to either: Arm 1: Adjuvant RT (64Gy in 32#)
commenced within 4 months of RP, or Arm 2: Active surveillance with 3
monthly PSA tests and commencement of early salvage RT (64Gy in 32#) if
PSA rises � 0.20 ng/ml. Stratification is by seminal vesicle invasion,
Gleason Score, pre-operative PSA, margin positivity (no/yes) and radiotherapy
institution. A sample size of 470 patients is required to detect a
10% non-inferiority margin in the 5-year biochemical failure-free rate
between the adjuvant and active surveillance arms. As of 31 Jan 2012,
186 patients have been recruited across 26 centres in Australia and New
Zealand. A meta analysis with the MRC RADICALS and GETUG-17 trials
will be prospectively designed to detect a survival difference between the
two approaches.
TPS4692^ General Poster Session (Board #16C), Sun, 8:00 AM-12:00 PM
Comparison of two doses of cabazitaxel plus prednisone in patients (pts)
with metastatic castration-resistant prostate cancer (mCRPC) previously
treated with a docetaxel (D)-containing regimen. Presenting Author: Mario
A. Eisenberger, Sidney Kimmel Comprehensive Cancer Center at Johns
Hopkins University, James Buchanan Brady Urological Institute, Baltimore,
MD
Background: The phase III TROPIC study (NCT00417079) reported a
significant improvement in overall survival (OS) for cabazitaxel (Cbz) �
prednisone (P;CbzP) (25 mg/m2 IV Q3W/10 mg PO QD) vs mitoxantrone
(M) � P (MP) (median OS 15.1 vs 12.7 mos; HR 0.70; P � 0.0001) in pts
with mCRPC (also known as hormone-refractory prostate cancer) previously
treated with a D-containing regimen. CbzP is approved by the FDA, EMA
and other health authorities for the treatment of pts with mCRPC that has
progressed after a D-containing regimen. Cbz toxicity is consistent with
other taxanes; compared with M, more hematologic toxicities are reported
(primarily Grade 3–4 neutropenia). Phase I/II studies identified 20 and 25
mg/m2 as recommended doses; 25 mg/m2 was selected for the phase III
TROPIC study. As pooled data show Grade 3–4 neutropenia incidence is
lower with Cbz � 25 mg/m2 (61%) vs � 25 mg/m2 (74%), it is of interest to
assess if reducing the Cbz approved dose in mCRPC lessens hematologic
toxicity and is non-inferior in terms of efficacy. Methods: PROSELICA
(NCT01308580) is a randomized, open-label, multinational, phase III
study comparing 20 mg/m2 and 25 mg/m2 Cbz for efficacy and tolerability.
Pts with a life expectancy � 6 mos, ECOG PS � 2, histologically/
cytologically confirmed metastatic prostate adenocarcinoma resistant to
hormone therapy and previously treated with a D-containing regimen are
eligible. Pts are randomized 1:1 to receive Cbz 20 mg/m² or 25 mg/m² IV
Q3W � P 10 mg PO QD, treated until disease progression, unacceptable
toxicity or withdrawal of consent (max 10 cycles), and stratified according
to ECOG PS, measurable disease (yes/no) and region. The primary endpoint
is OS (non-inferiority design). Secondary endpoints include safety, progression-free
survival (PCWG2 criteria), PSA and pain progression and response,
tumor response in pts with measurable disease and health-related
quality of life. Cbz PK and pharmacogenomics will be assessed in pt
subgroups. Planned enrollment is 1,200 pts. Study start was in May 2011;
as of Jan 2012, 270 pts had been enrolled. The first DMC meeting
recommended continuing the study without change.
TPS4691 General Poster Session (Board #16B), Sun, 8:00 AM-12:00 PM
CA184-095: A randomized, double-blind, phase III trial to compare the
efficacy of ipilimumab versus placebo in asymptomatic or minimally
symptomatic patients (pts) with metastatic chemotherapy-naive castrationresistant
prostate cancer (CRPC). Presenting Author: Tomasz M. Beer,
Oregon Health & Science University Knight Cancer Institute, Portland, OR
Background: Ipilimumab (Ipi), a fully human monoclonal antibody which
blocks CTLA-4, augments antitumor immune responses. Ipi has demonstrated
overall survival (OS) benefit in two Phase 3 trials for advanced
melanoma, with side effects that were managed using product-specific
treatment guidelines. In addition, in Phase 1/2 trials in metastatic CRPC,
Ipi has shown clinical activity (as measured by prostate-specific antigen
[PSA] declines and RECIST response) with no unexpected toxicities. While
docetaxel is standard therapy for metastatic CRPC, its use may be delayed
until pts develop symptoms. As such, this global (~150 sites in 25
countries) Phase 3 study (ClinicalTrials.gov identifier: NCT01057810) is
evaluating Ipi vs placebo in chemotherapy-naïve pts with asymptomatic or
minimally symptomatic CRPC without visceral metastases. Methods: The
primary endpoint is OS; secondary endpoints include progression-free
survival, time to pain progression, and time to non-hormonal systemic
therapy. The study is designed to detect a 9.3 month difference (HR�0.7)
in OS with 90% power and 0.05 two-sided significance. Pts are randomized
at a 2:1 ratio to receive Ipi 10 mg/kg every 3 weeks for up to 4 doses or
placebo, respectively, as induction therapy. Eligible pts will continue to
receive maintenance therapy of blinded study drug every 12 weeks until
treatment stopping criteria are met, withdrawal of consent, or study
closure. The accrual goal is 600 pts randomized.
Inclusion criteria
Metastatic CRPC
Asymptomatic or minimally symptomatic
Progression during prior hormonal therapy
Discontinuation of anti-androgens
Testosterone < 50 ng/dl
ECOG Performance Status 0-1
Exclusion criteria
Liver, lung, or brain metastases
Prior immunotherapy or chemotherapy for metastatic CRPC
Autoimmune disease
HIV, Hep B, or Hep C infection
Pelvic targeted radiotherapy within 3 months of study
TPS4693 General Poster Session (Board #16D), Sun, 8:00 AM-12:00 PM
A phase III, randomized, double-blind, multicenter trial comparing the
investigational agent orteronel (TAK-700) plus prednisone (P) with placebo
plus P in patients with metastatic castration-resistant prostate cancer
(mCRPC) that has progressed during or following docetaxel-based therapy.
Presenting Author: Robert Dreicer, Cleveland Clinic, Cleveland, OH
Background: The investigational agent orteronel is a selective inhibitor of
17,20-lyase, a key enzyme in the testosterone synthesis pathway. In a
phase 1/2 study in men with mCRPC, orteronel reduced prostate-specific
antigen (PSA) levels, and inhibited testosterone and DHEA-S consistent
with potent 17,20-lyase inhibition (Agus D, et al. J Clin Oncol 2012;30:s5
abst 98). Docetaxel-based chemotherapy is an effective but noncurative
therapy for mCRPC that has progressed on hormonal therapy; new therapeutic
options are needed. Methods: This double-blind, multicenter study is
assessing orteronel � P vs placebo � P in men with mCRPC
(NCT01193257; C21005). Patients must have evidence of disease progression
during or after receiving a total of �360 mg/m2 docetaxel within a
6-mo period. Patients who are clearly intolerant to docetaxel or have
progressive disease before receiving �360 mg/m2 are also eligible if they
have received at least 225 mg/m2 of docetaxel within a 6-mo period and
meet the other inclusion criteria. Other eligibility criteria include radiographically
documented metastatic disease and baseline testosterone �50 ng/dL
following surgical or medical castration. Prior adrenal-targeted therapies
are not permitted. Men may have opioid-requiring bone pain. The planned
sample size is 1083; men will be randomized 2:1 to receive orteronel 400
mg twice daily (BID) plus P5mgBIDorplacebo plus P. The primary
endpoint is overall survival; other endpoints are radiographic progressionfree
survival, PSA decrease of �50% at 12 wks, pain response at 12 wks,
safety, time to PSA progression, objective response by RECIST, circulating
tumor cell and endocrine marker changes, and patient-reported outcomes.
After disease progression, men may continue to receive study drug. Tumor
specimens will be analyzed for biomarkers that may predict orteronel
antitumor activity, including the TMPRSS2:ERG fusion gene. The same
regimens are being evaluated in a concurrent phase 3 study in chemotherapy-naïve
men with mCRPC (NCT01193244).
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