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

300s Genitourinary Cancer
4593 General Poster Session (Board #3H), Sun, 8:00 AM-12:00 PM
Activity of intravesical CG0070 in Rb-inactive superficial bladder cancer
after BCG failure: Updated results of a phase I/II trial. Presenting Author:
Terence W. Friedlander, University of California, San Francisco, San
Francisco, CA
Background: Loss of retinoblastoma (Rb) tumor suppressor activity occurs
commonly in bladder cancer and leads to upregulation of the E2F-1
transcription factor. CG0070 is a replication-competent oncolytic adenovirus
genetically modified to express GMCSF under control of the human
E2F-1 promoter. Updated results from a phase I study of CG0070 in
patients with recurrent superficial bladder cancer (T1, Ta, Tcis) after BCG
treatment are presented here. Methods: The V-0046 phase I/II study
previously reported the safety and evidence of efficacy of single and
multiple doses of intravesical CG0070. Efficacy was determined using
quarterly cystoscopy, biopsy, and/or urine cytology. Tumor Rb status was
assessed immunohistochemically in 18 tumors. Results: 35 patients were
treated with either a single dose (n�13) of CG0070 ranging from 1x1012 to
3x1013 viral particles (vp) or with weekly x6(n�9) or every 4 week x 3-6
doses (n�13) ranging from 1x1012 to 1x1013 vp per dose. The most
common adverse events regardless of schedule were flu-like illness,
dysuria, hematuria, bladder spasm, and nocturia. No maximum tolerated
dose was reached. Urine GMCSF and CG0070 levels were detectable in
almost all patients suggesting in-vivo viral replication. The CR rate in the
single dose cohort was 23% (3/13), and 64% (14/22) in the multi-dose
cohorts. The CR rate for patients with either CIS or Ta tumors was 65%
(15/23). Of all responders, 11 recurred with a remission duration ranging
from 3.0 - 33.4 months and 6 patients, all in the multiple dose cohorts,
remain in remission as of last follow-up with a remission duration ranging
from 3.3 – 38.2 months. Phosphorylated (inactive) Rb was detected in 13
of the 18 (72%) patients evaluated. Nine of these 13 patients (70%) had a
complete response. All patients (5/5, 100%) with known phosphorylated
Rb treated in the weekly cohort experienced a CR. Conclusions: CG0070
was well tolerated with minimal toxicities. Complete responses were more
frequently observed in the multiple-dose cohorts, including durable CRs in
patients with inactive Rb and in patients with CIS. Further study in
Rb-inactive superficial tumors is warranted.
4595 General Poster Session (Board #4B), Sun, 8:00 AM-12:00 PM
Late gastrointestinal (GI) complications in patients with stage I-II testicular
seminoma treated with radiotherapy (RT). Presenting Author: Christopher
Leigh Hallemeier, Mayo Clinic, Rochester, MN
Background: For stage I-II testicular seminoma, RT is highly effective at
eradicating disease in the abdominopelvic lymph nodes, but results in
unnecessary exposure to normal tissues including the GI tract. The purpose
of this study was to define the incidence and risk factors for late GI
complications in this patient population. Methods: A retrospective review
was performed of 251 patients with stage I-II testicular seminoma treated
with curative intent RT at our institution from 1974-2009. All patients
underwent orchiectomy and postoperative external beam RT to the involved
and/or at-risk nodal basins. Potential late GI complications that were
assessed included endoscopically-confirmed gastric or duodenal ulceration,
small bowel obstruction (SBO), and biopsy-confirmed malignancy of
the GI tract. Risks were estimated using the Kaplan-Meier (KM) technique
and univariate/multivariate analyses were performed using the Cox proportional
hazards model. Results: Median age at diagnosis was 36 years (range
18 – 80). Clinical stage was I (n�199) or II (n�52). Median abdominopelvic
RT dose was 26 Gy (interquartile range 25 – 30). Median follow-up was
15 years (range 0.1 – 38). KM estimates for any GI complication (ulcer,
SBO, or GI malignancy) at 10, 20, and 30 years were 7, 10 and 24%,
respectively. Four patients died as result of a GI complication. KM
estimates for ulcer at 10, 20, and 30 years were 4, 7, and 9%, respectively.
Age at RT (Hazard Ratio [HR] 1.05, 95% Confidence Interval [CI] 1.00 –
1.10, p�0.03) and RT total dose (per Gy, HR 1.20, 95% CI 1.09 – 1.31,
p�0.01) were associated with risk of ulcer. KM estimates for SBO at 10,
20, and 30 years were 2%, 2%, and 3%, respectively. History of
inflammatory bowel disease was associated with risk of SBO (HR 43, 95%
CI 7-325, p�0.01). KM estimates for GI malignancy at 10, 20, and 30
years were 0.5, 3 and 16%, respectively. Age at RT was associated with risk
of GI malignancy (HR 1.07, 95% CI 1.02-1.14, p�0.01). Conclusions: In
patients with stage I-II testicular seminoma treated with RT, late GI
complications were a relatively uncommon, but clinically significant source
of late morbidity. Use of low dose, limited field, and/or proton RT may
reduce these risks.
4594 General Poster Session (Board #4A), Sun, 8:00 AM-12:00 PM
Utilization and predictors of neoadjuvant chemotherapy for muscleinvasive
bladder cancer in the Veterans Health Administration. Presenting
Author: Gurdarshan Singh Sandhu, Washington University School of
Medicine, St. Louis, MO
Background: The survival benefit with neoadjuvant chemotherapy for
bladder cancer was established in 2003. However, adoption of this
paradigm in clinical practice has been slow. We explored the use of
neoadjuvant chemotherapy and identified predictors of its use in a
contemporary cohort in the Veterans Health Administration (VA). Methods:
Using the national VA Clinical Cancer Registry, all patients diagnosed with
clinical stage T2-4, N0 or Nx, M0 bladder cancer from 1997 to 2007 were
stratified into surgically (radical cystectomy [RC], n�1,211) and nonsurgically
managed groups (n�2,125). Receipt of neoadjuvant chemotherapy
was defined as chemotherapy treatment up to 6 months before RC as well
as initial treatment only with chemotherapy (without subsequent surgery or
radiation) in the nonsurgical group. Temporal trends in neoadjuvant
chemotherapy use were evaluated with a chi square test. Predictors of
neoadjuvant chemotherapy were examined using a multivariable logistic
regression model incorporating demographic, socioeconomic, comorbid,
pathologic and hospital factors. Results: 6.3% and 8.3% of patients
received neoadjuvant chemotherapy in the surgical and non-surgical group,
respectively. Analysis of temporal trends in chemotherapy use demonstrated
an increase in neoadjuvant chemotherapy use over time (p�0.0001);
from 3% (2003 and before) to 14% annually (2007). On multivariable
analysis of both groups, older age and more recent diagnosis were
predictive of neoadjuvant chemotherapy use (Table). Other covariates did
not predict receipt of neoadjuvant chemotherapy. Conclusions: While
overall use of neoadjuvant chemotherapy in the VA population with bladder
cancer remains low, use thereof is slowly increasing, with a more recent
diagnosis most strongly predicting its use.
Multivariable predictors of neoadjuvant chemotherapy in bladder cancer.
OR 95% CI P value
Age (per year older)
Year of diagnosis (reference 2003 and before)
1.02 1.00-1.04 �.0001
2004 1.56 0.98-2.47 0.06
2005 1.23 0.76-2.00 0.39
2006 1.66 1.09-2.52 0.02
2007 2.38 1.59-3.57 �0.0001
4596 General Poster Session (Board #4C), Sun, 8:00 AM-12:00 PM
Interim results of phase II trial of the cyclin-dependent kinase 4/6 inhibitor
PD-0332991 in refractory retinoblastoma protein positive germ cell
tumors. Presenting Author: David J. Vaughn, Abramson Cancer Center at
the University of Pennsylvania, Philadelphia, PA
Background: Deregulation of the retinoblastoma pathway in germ cell
tumors (GCT) has been well documented. We previously reported that
PD-0332991, a selective oral inhibitor of cyclin-dependent kinase 4/6, led
to prolonged disease control in 3 patients (pts) with unresectable growing
teratoma syndrome (NEJM, 2009). For these reasons, we initiated a phase
II trial of PD-0332991 in pts with refractory retinoblastoma protein (Rb)
positive (�) GCT. Methods: Pts with incurable refractory GCT that expressed
Rb by immunohistochemistry were treated with PD-0332991 125 mg
orally daily for 21 days followed by a 7 day break (cycle � 28 days). Tumor
assessments were performed every 2 cycles. The primary endpoint was
6-month progression-free survival (PFS) rate. Results: As of 1/12/2012,
archived tumors from 36 pts with refractory GCT were stained for Rb and 35
had � 1� staining. 18 of planned 24 pts have been enrolled and treated.
Pt characteristics: 17 male, 1 female; median age, 31 years (range,
17-56); median ECOG performance status, 1 (range, 0-1); median number
of prior chemotherapy regimens, 2 (range, 1-6); median number prior
surgeries, 3 (range, 1-6). Pt pathology: mature teratoma (MT), 7; teratoma
with malignant transformation (TMT), 7; mixed GCT, 2; late relapse (LR),
2. 16 pts are evaluable; 2 pts are too early to evaluate. 5 of 16 evaluable pts
achieved 6-month PFS (3 MT, 1 TMT, 1 LR). Median PFS was 2 months
(range, 0-17). No objective radiological responses were observed; 7
patients had best response of stable disease by RECIST criteria (3 MT, 3
TMT, 1 LR). Grade 3 toxicity included neutropenia (4 pts), thrombocytopenia
(3 pts), anemia (1 pt), mucositis (1 pt). No grade 4 toxicity was seen.
Analysis of archival tumor for predictive biomarkers including Rb and p16
expression is being performed. Conclusions: PD-0332991 has resulted in
6-month PFS in pts with refractory Rb � GCT, including pts with incurable
teratomas.
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