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

4670 General Poster Session (Board #13E), Sun, 8:00 AM-12:00 PM
African American race to predict for earlier failure of active surveillance:
Results from the Duke Prostate Center. Presenting Author: Mitchell
Bassett, Duke University Medical Center, Durham, NC
Background: As concerns mount regarding overtreatment and overdiagnosis
of prostate cancer (CaP), active surveillance (AS) is increasingly
utilized in low risk patients. While African-American (AA) race is associated
with adverse outcomes after prostatectomy, its effect on patients managed
with AS is not known. Methods: A retrospective review identified 222
patients managed with AS at the Duke Prostate Center from January 2005
to September 2011. All men had CaP diagnosed on biopsy performed at our
center, and elected AS over treatment. Failure was defined as progression
to treatment. In men who failed AS, the reasons for failure, follow-up PSA
and biopsy characteristics were analyzed. The primary outcome - time from
diagnosis to failure of AS for a reason other than patient choice - was
analyzed with univariable and multivariable Cox proportional hazards
models. Results: In our AS cohort, 73% are Caucasian and 23% AA. Median
follow-up is 25.4 months. Age, household income, BMI, PSA, clinical
stage, family history, prostate volume, number of cores with cancer, and
Gleason grade on initial biopsy did not differ by race. The number of
biopsies and PSA tests performed on AS did not differ by race. A higher
proportion of AA men tended to fail from biopsy progression (72.7% vs.
63.8%) while a lower proportion failed by choice (9.1% vs. 14.9%)
compared to Caucasians (p � 0.114). AA men had a significantly shorter
time to failure (HR 1.74, p � 0.045) compared to Caucasians. There was a
trend toward increased Gleason grade 8 or higher cancer on follow-up
biopsy in AA compared to Caucasian men (10% vs. 2.5%, p � 0.08). AA
race remained a predictor (HR 1.76, p � 0.058) of failure on multivariable
analysis, as did initial PSA (HR 1.90, p � 0.031) and number of cores with
cancer on initial biopsy (HR 1.29, p � 0.013). Conclusions: AA race was
associated with higher risk for failure of AS. There was a trend toward AA
men failing due to biopsy progression and with higher grade cancer.
Additional follow-up is necessary to determine how this affects the long
term outcomes of these men.
TPS4672 General Poster Session (Board #13G), Sun, 8:00 AM-12:00 PM
Phase II trial of cabazitaxel in patients with advanced or metastatic
transitional cell carcinoma of the urothelial tract who have progressed
within less than 12 months after cisplatin-based chemotherapy: A Spanish
Oncology Genitourinary Group (SOGUG) study. Presenting Author: Jose
Angel Arranz Arija, Hospital General Universitario Gregorio Marañón,
Madrid, Spain
Background: Advanced transitional cell carcinoma of the urothelium (TCCU)
on progression after previous cisplatin-based combination is generally an
incurable disease. The appropriate management of these patients is still an
unmet need. Many drugs have shown modest or no activity in previous
phase 2 trials. Population heterogeneity in these studies emerges as one of
the key determinants that could explain the variable outcomes. Recently, in
a phase III study in this setting, prognostic factors (PF) for overall survival
were identified (Bellmunt J et al, JCO 2010). Taxanes are active drugs in
2nd-line metastatic TCCU. Cabazitaxel (C) is a semi-synthetic taxane that
is a poor substrate for the multidrug resistance system. C could be a valid
alternative in this patient population. Methods: This is an open label phase
II study of C in patients (pts) with advanced or metastatic TCCU who have
progressed within 12 months after receiving a 1st-line platinum based
chemotherapy. There are three treatment arms as patients will be assigned
to one of three groups previously defined based on the presence of 0, 1 or
2-3 PFs as defined by Bellmunt et al. The activity of C will be assessed
separately in each group and overall. The primary endpoint is response rate
(RR) evaluated according to RECIST 1.1, a maximum of 35 pts are needed
in each subgroup (maximum number of pts required: 105). Secondary
objectives are RR in the whole population, toxicity, progression-free
survival and overall survival. In addition, an external validation of the
prognostic model proposed by Bellmunt will be conducted, as well as a
pharmacogenomic study in order to better define the toxicity profile of the
drug and the potential responders.
Genitourinary Cancer
319s
4671 General Poster Session (Board #13F), Sun, 8:00 AM-12:00 PM
Activity of oral VT-464, a selective CYP17-lyase inhibitor, in the LNCaP
prostate cancer xenograft. Presenting Author: William Douglas Figg,
Medical Oncology Branch, National Cancer Institute, National Institutes of
Health, Bethesda, MD
Background: With the FDA approval of abiraterone acetate, inhibition of
CYP17 (17� hydroxylase/C17, 20-lyase) is now a validated approach to the
treatment of castration-resistant prostate cancer. VT-464 is a novel,
selective CYP17-lyase inhibitor with decreased activity against CYP17
hydroxylase (less mineralcocorticoid and glucocorticoid effects). The study
objectives were to observe the effects of VT-464 in a prostate cancer
xenograft model and to compare its activity to abiraterone acetate and
surgical castration. Methods: SCID mice were implanted subcutaneously
with LNCaP cells. When tumors reached 100 mm3 , mice were randomized
to receive vehicle (0.5% CMC in saline, 5 mL/kg), VT-464 at 15, 50, or 100
mg/kg p.o. b.i.d. A second cohort of LNCaP tumor-bearing mice received
vehicle, surgical castration, or VT-464, or abiraterone acetate at 100 mg/kg
p.o. b.i.d. for 28 days. Terminal blood and tumor concentrations were
analyzed on day 28, four hours after the last dose. Results: In the first
LNCaP xenograft cohort, percent growth inhibition (� S.E.) of 9.6 (�15.6),
38.5 (�12.4), and 73.9 (�13.2) was observed on day 21 of treatment for
VT-464 doses of 15, 50, and 100 mg/kg, respectively. Growth reduction at
100 mg/kg was statistically significant compared to vehicle control from
day 7 to 28. VT-464 was well tolerated with insignificant weight loss at all
doses. In the second cohort, VT-464-treated (100 mg/kg) mice had
significantly reduced tumor volumes on day 28 compared to control and
abiraterone acetate (p�0.05, p�0.01, respectively). Reduction in tumor
volumes were similar between VT-464-treated (100 mg/kg) and castrate
animals. Plasma and tumor analyses revealed much greater plasma and
tumor exposure of VT-464 compared to abiraterone acetate. Conclusions:
VT-464 exhibited dose-dependent growth inhibition with significantly
reduced tumor volumes at the highest dose compared to abiraterone
acetate. The activity in VT-464-treated animals was similar to that of
castrate animals. These preclinical results show promising activity of
VT-464 in the treatment of prostate cancer.
TPS4673 General Poster Session (Board #13H), Sun, 8:00 AM-12:00 PM
Design of a phase II randomized, open-label trial of DN24-02, an
autologous cellular immunotherapy targeting HER2/neu, in patients with
surgically resected urothelial cancer at high risk of recurrence. Presenting
Author: Dean F. Bajorin, Memorial Sloan-Kettering Cancer Center, New
York, NY
Background: Despite surgical resection and the use of (neo)adjuvant
chemotherapy, up to 50% of patients with invasive urothelial carcinoma
will have disease recurrence and eventually die of metastatic disease. New
approaches are needed for these patients. Approximately 50% of patients
with high-risk pathologic features have evidence of HER2 expression in the
primary tumor or involved lymph nodes. DN24-02 is an autologous cellular
immunotherapy targeting HER2, which is based on Dendreon’s Antigen
Delivery Cassette technology – the same platform used for sipuleucel-T (an
FDA-approved treatment for asymptomatic or minimally symptomatic
metastatic castrate-resistant prostate cancer). Each dose of DN24-02 is
manufactured by culture of peripheral blood mononuclear cells obtained by
leukapheresis with a recombinant antigen that comprises components of
the intra- and extracellular domains of the HER2 antigen linked to GM-CSF.
A product similar to DN24-02 has shown evidence of safety and immune
response in phase I studies. Objectives: The primary objective is to
determine whether DN24-02, given as adjuvant therapy following surgical
resection, can prolong survival compared to standard of care (SOC).
Secondary objectives are to evaluate disease-free survival, safety, and
immune responses to DN24-02. Methods: Eligible patients will have
undergone surgical resection of a primary urothelial cancer, with either
�pT2 or pN� staging, and HER2 expression �1� by IHC based on
pathologic review. Approximately 180 patients will be randomized (1:1) to
receive three IV infusions of DN24-02 as adjuvant therapy approximately
every 2 weeks, or SOC. Stratification will include 1) neoadjuvant chemotherapy
vs surgery alone; and 2) positive (pN�) vs negative lymph node
involvement (pN0). Other adjuvant chemotherapy will not be allowed.
Patients can be treated per SOC if there is disease recurrence. Patients will
be monitored for evidence of recurrence by imaging, and followed for
survival. Cellular and serological immune responses will be assessed at
baseline and post-DN24-02 therapy.
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