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

4516 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
A validated whole-blood RNA transcript-based prognostic model that
predicts survival in men with castration-resistant prostate cancer. Presenting
Author: William K. Oh, Division of Hematology and Medical Oncology,
The Tisch Cancer Institute, Mount Sinai School of Medicine, New York, NY
Background: Survival for patients with castration resistant prostate cancer
(CRPC) is highly variable. We developed a whole blood RNA transcriptbased
model as a prognostic biomarker in CRPC. Methods: Peripheral blood
was collected from 62 men with CRPC in a training set and from 140
patients with CRPC in a validation set on various treatment regimens. A
panel of 168 inflammation and prostate cancer-related genes was evaluated
using optimized quantitative polymerase chain reaction to assess
biomarkers predictive of survival. A 2-class proportional hazard model was
developed from time of CRPC diagnosis and time of blood draw. Results: A
6-gene model (consisting of ABL2, SEMA4D, ITGAL, and C1QA, TIMP1,
CDKN1A) separated CRPC patients into two classes: higher risk men who
died within 2·2 years of developing CRPC and lower risk men who lived over
2·2 years (log rank p�0·00083). The results were similar regardless of the
survival time definition (CRPC diagnosis versus blood draw) and did not
depend on whether they received chemotherapy in addition to hormone
treatment. The model successfully validated in an independent cohort of
men with CRPC (p� 0.000001·7). Conclusions: Transcriptional profiling of
whole blood yields critical prognostic information in men with CRPC
independent of treatment. The 6-gene model suggests possible dysregulation
of the immune system, a finding that warrants further study. This
model may play an important role in patient counseling, in patient
stratification for clinical trials, and potentially as a predictive biomarker for
immune-based therapeutic strategies.
LBA4518 Clinical Science Symposium, Sat, 8:00 AM-9:30 AM
Interim analysis (IA) results of COU-AA-302, a randomized, phase III study
of abiraterone acetate in chemotherapy-naive patients (pts) with metastatic
castration-resistant prostate cancer (mCRPC). Presenting Author: Charles
J. Ryan, University of California, San Francisco, San Francisco, CA
The full, final text of this abstract will be available at
abstract.asco.org at 12:01 AM (EDT) on Saturday, June 2,
2012, and in the Annual Meeting Proceedings online
supplement to the June 20, 2012, issue of Journal of
Clinical Oncology. Onsite at the Meeting, this abstract will
be printed in the Saturday edition of ASCO Daily News.
Genitourinary Cancer
281s
4517 Oral Abstract Session, Tue, 9:45 AM-12:45 PM
18F-16�-fluoro-5�-dihydrotestosterone (FDHT) PET as a prognostic biomarker
for survival in patients with metastatic castrate-resistant prostate
cancer (mCRPC). Presenting Author: Karen A. Autio, Memorial Sloan-
Kettering Cancer Center, New York, NY
Background: At present there is no imaging biomarker for patients with
mCRPC as the disease primarily metastasizes to bone, which is difficult to
visualize and quantify using standard techniques. We have conducted
clinical trials in which patients with progressive mCRPC are scanned using
FDG-PET to examine glucose metabolism, and FDHT-PET. FDHT is a novel
tracer and structural analog of dihydrotestosterone that binds to the
androgen receptor (AR) to demonstrate AR overexpression, a key biologic
feature of mCRPC. We previously reported an association between baseline
FDG-PET and overall survival in mCRPC. We now present the prognostic
utility of baseline FDHT-PET. Methods: We prospectively scanned mCRPC
patients with FDG and FDHT-PET prior to a change in therapy as part of
imaging clinical trials. PET results were represented as the hottest lesion
(SUVmax), or average of the five hottest lesions (SUVmaxavg). Five lesions
per patient were recorded. If less than 5 lesions were captured, a value of 1
was imputed for the remaining lesions. Clinical and lab parameters were
collected. Univariate analysis was performed on PET, clinical and lab
variables for association with overall survival (OS). Multivariate models of
prognostic factors were constructed. Results: 170 mCRPC patients were
imaged with FDG and 116 also had FDHT-PET at baseline. Median survival
was 21.2 months (95%CI: 19.1-24.0). On univariate analysis, FDHTmax,
FDHTmaxavg, FDGmaxavg, PSA, hemoglobin, alkaline phosphatase, and
LDH were associated with OS. FDHTmax and FDHTmaxavg were significantly
correlated with one another. In a multivariate model, FDHTmaxavg
and LDH were prognostic of survival. In a separate model assessing FDG,
FDGmaxavg and LDH were also prognostic. Conclusions: FDHT not only
allows for a visual assessment of the AR axis in prostate cancer, but appears
to associate with overall survival in mCRPC. Increased AR activity as
measured by FDHT SUVmaxavg held greater prognostic value than PSA or
Gleason score. FDHT is also being evaluated as a clinical response indicator
and pharmacodynamic measure with AR directed therapies.
4519^ Clinical Science Symposium, Sat, 8:00 AM-9:30 AM
Primary, secondary, and quality-of-life endpoint results from the phase III
AFFIRM study of MDV3100, an androgen receptor signaling inhibitor.
Presenting Author: Johann Sebastian De Bono, The Institute for Cancer
Research, London, United Kingdom
Background: MDV3100, a novel androgen receptor signaling inhibitor
(ARSI), inhibits: 1) binding of androgens to AR, 2) AR nuclear translocation,
and 3) association of AR with DNA. MDV3100 was active in a phase
I-II trial enrolling pre- and post-docetaxel castration-resistant prostate
cancer (CRPC) patients. The AFFIRM trial evaluated whether MDV3100
could provide benefit to men with post-docetaxel CRPC. Methods: In this
double-blind, multinational phase III study, patients who had received
docetaxel-based chemotherapy were randomized 2:1 to MDV3100 160
mg/day or placebo. Treatment with corticosteroids was allowed but not
required. Patients were stratified by baseline ECOG and mean brief pain
inventory score. The primary endpoint was overall survival (OS). Other
efficacy endpoints included radiographic progression-free survival (rPFS),
time to PSA progression (TTPP), soft tissue objective response (PR�CR),
PSA response, and quality of life (QoL) response (FACT-P). Results: 800
patients were randomized to MDV3100 and 399 to placebo with respective
median treatment durations of 8.3 and 3.0 months.Based on a planned
interim analysis at 520 deaths, the Independent Data Monitoring Committee
recommended the study be unblinded and placebo patients offered
MDV3100. Efficacy results are presented (Table). The most common
MDV3100 events with an incidence higher than placebo were fatigue (34%
vs 29%), diarrhea (21% vs 18%), and hot flush (20% vs 10%). Grade �3
events of interest were cardiac disorders (0.9% MDV3100 vs 2% placebo),
fatigue (6% MDV3100 vs 7% placebo), seizure (0.6% MDV3100 vs. 0%
placebo), and LFT abnormalities (0.4% MDV3100 vs 0.8% placebo).
Conclusions: MDV3100, a novel ARSI, is well-tolerated and significantly
prolongs OS, slows disease progression, and improves QoL in men with
post-docetaxel CRPC.
MDV3100 Placebo HR (95% CI) P value
OS, median 18.4 months 13.6 months 0.631 (0.529, 0.752) �0.0001
rPFS, median 8.3 months 2.9 months 0.404 (0.350, 0.466) �0.0001
TTPP, median 8.3 months 3.0 months 0.248 (0.204, 0.303) �0.0001
PR�CR 25.1%� 3.8% 2.9%�1.0% - �0.0001
PSA response 54.0% 1.5% - �0.0001
QoL response 43.3% 17.8% - �0.0001
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