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

294s Genitourinary Cancer
4569 Poster Discussion Session (Board #23), Mon, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Dual antiangiogenic therapy using lenalidomide and bevacizumab with
docetaxel and prednisone in patients with metastatic castration-resistant
prostate cancer (mCRPC). Presenting Author: Bamidele Adesunloye, Medical
Oncology Branch, National Cancer Institute, National Institutes of
Health, Bethesda, MD
Background: Previously, we had shown the potent anti�tumor activity of
dual anti-angiogenic therapy by combining bevacizumab (B) and thalidomide
(T) with docetaxel (D) and prednisone (P) in mCRPC (Ning JCO
2010). We hypothesized that combining lenalidomide (L), an analogue of
T, with B, D, and P would have a more favorable efficacy/toxicity profile.
Methods: All patients (pts) had chemotherapy�naïve mCRPC. Among the
first 52 pts, 3 received L 15 mg daily, 3 had 20 mg daily, and the rest had
25 mg daily for 14 days of every 21�day cycle (C). The protocol was
recently amended to enroll 11 more pts at L 15 mg; 2 pts have now been
enrolled in this expansion cohort. All pts received D 75 mg/m2 and B 15
mg/kg on day 1 with P 10 mg and enoxaparin daily throughout each C.
Pegfilgrastim was given on day 2. PSA each C with imaging after C2 and
after every 3C. Dental exams with mandible CT scan at baseline, after C5,
and every 6C. Results: 54 of 62 pts have been enrolled. Median age 65.5
(51�82), Gleason score 8 (5�10), on�study PSA 85.2 ng/ml
(0.15�3520), and pre�study PSA doubling time 1.49 months
(0.52�6.73). Median number of Cs was 16 (3�38). PFS was 22 months
and probability of survival at 12 months was 90%. Forty-six (85.2%) and
42 (77.8%) pts had PSA declines of �50% and �75%, respectively. Of 30
pts with measurable disease there were 1 CR and 25 PR (86.7% overall
RR). 17/54 pts were off study for radiographic disease progression and
8/54 for other reasons. Grade �2 toxicities included neutropenia (34/54),
anemia (23/54), thrombocytopenia (7/54), hypertension (12/54), perianal
fistula (3/54), rectal fissure (1/54), myocardial infarction (1/54), and
osteonecrosis of the jaw (ONJ) (12/54, 22.0%). At the time of diagnosis of
ONJ, 7/12pts were on bisphosphonates (BP), 2/12 had used BP previously,
and 3/12 never used BP. The incidence of ONJ was comparable to 18.3%
reported by Ning et al. A recent study of carboplatin plus weekly docetaxel
reported an incidence of 29.3%. Conclusions: Dual anti-angiogenic therapy
with, B and L, plus D and P was associated with high PSA (85.2%) and
tumor (86.7%) responses in mCRPC, with manageable toxicities. The
incidence of ONJ is comparable to other studies.
4571 Poster Discussion Session (Board #25), Mon, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
Preliminary quality-of-life outcomes for SWOG-9346: Intermittent androgen
deprivation in patients with hormone-sensitive metastatic prostate
cancer (HSM1PC)—Phase III. Presenting Author: Carol Moinpour, Fred
Hutchinson Cancer Research Center, Seattle, WA
Background: The relative quality of life (QOL) for patients with newly
diagnosed, metastatic prostate cancer, treated with intermittent androgen
deprivation (IAD) has been assumed and hypothesized, yet never compared
in a well-powered randomized trial (RT) to continuous androgen deprivation
(CAD). SWOG-9346 provided such a RT in which to test QOL differences
between CAD and IAD in men with metastatic prostate cancer. Methods:
Patients were randomized to CAD or IAD. Patients completed the SWOG
QOL Questionnaire (SF-20/SF-36, Symptom Distress Scale, treatmentspecific
symptoms, global QOL) at randomization and months (mo) 3, 9,
and 15 post-randomization. Five QOL change scores at one time point (mo
3) were designated as primary for the QOL endpoint and are reported in this
abstract: impotence, libido, energy/vitality (E/V), physical function (PF),
and emotional function (EF). Significance level was adjusted for 5
comparisons (used p�0.01). Results: 615 patients in the CAD arm and
633 in the IAD arm completed the QOL questionnaire at baseline. Change
between baseline and 3 months differed for the two arms with CAD
reporting statistically significantly more impotence and less libido than
IAD. EF was also slightly better for the IAD arm. Conclusions: These results
indicate better sexual function in men receiving IAD versus CAD through
post-randomization month 3. Additional benefits for IAD may include
better PF, E/V and EF. Ongoing analyses will address the role of missing
data, additional follow-up assessments, and resumption of therapy in the
IAD arm.
Baseline treatment arm
Impotence %
(n)
Libido %
(n)
EF^ score
(n)
PF^ score
(n)
E/V^ score
(n)
Descriptive results
3-mo
CAD IAD CAD IAD T-test p values*
.85
(546)
.03
(560)
80.0
(568)
70.2
(569)
59.8
(557)
.82
(585)
.04
(580)
77.9
(595)
70.7
(591)
59.7
(586)
.87
(487)
.04
(481)
79.0
(491)
69.3
489)
58.9
(478)
.73
(494)
.11
(486)
79.6
(500)
71.3
(500)
60.0
(489)
*T-test of arm difference in baseline to 3-month change for patients with both assessments; ^0-100 scale.
� 0.01
� 0.01
� 0.01
0.08
0.23
4570 Poster Discussion Session (Board #24), Mon, 8:00 AM-12:00 PM and
11:30 AM-12:30 PM
A multinational phase III adjuvant study of immediate (I) versus deferred
(D) chemotherapy (C)/hormone therapy (HT) after radical prostatectomy
(RP): TAX-3501. Presenting Author: Mario A. Eisenberger, Sidney Kimmel
Comprehensive Cancer Center at Johns Hopkins University, Baltimore, MD
Background: TAX 3501 was designed to test I or D C/HT after RP. No
adequately designed prospectively randomized surgical systemic adjuvant
studies have ever been successfully completed. Methods: TAX-3501 was a
randomized phase III study. Eligibility included post-operative predicted
probability of 5-year freedom from progression of �60% (Kattan et al)
after central pathology review, no prior C/HT, undetectable PSA, M0,
normal hematology/chemistries, signed consent. Pts were randomized
within 120 days after RP to I or D (at 1st progression) Rx with HT (leuprolide
acetate 22.5mg S.C. q.3 months x6)�/- C (docetaxel 75mg/m2 q.3wks x
6). F/U included a physical exam, PSA, CBC/chemical profile, serum T,
scans yearly or at progression (PSA� 0.4ng/ml, clinical or radiographic
and death). Main objectives comparing PFS and 5-year progression-free
rates after systemic treatment (2 � 2 factorial design, 4 arms). 1,696
subjects would provide 90% power to detect the targeted treatment effect
at a 5% 2-sided type I error level. Results: From 12/2005-9/2007399
pts were registered, 228 randomized after central path review ICHT�55,
IHT�55, DCHT�56, DHT�62, median age 62 (41-76), pre-op PSA
(ng/ml) 9.38 (2.2 - 90.0), Gleason score- 8,T3a (19.6%),
R�(65%),S.V.�(50%),N�(19.7%%), all had undetectable post op PSA.
Predicted probability of no progression was 21% on 228pts. Study was
terminated by sponsor (9/2007) due to poor accrual F/U continued from
2007-2010. Small sample size precludes reliable analyzes 37/118 (31.3%)
on the D arms received CHT/HT (all PSA progressions); ICHT 10/55, IHT
14/55, DCHT 9/56, DHT 8/62 met progression endpoint after I/D Rx (1/31
bone). AEs were characteristic and reversible (no grade 5). Leading causes
of accrual impediment were inadequate site selection, no consensus
regarding patient and treatment selection for this pt population, physician
and patient bias re: treatment and evolving changes in the adjuvant
treatment landscape during follow-up time (adjuvant RT). Conclusions: The
role of adjuvant systemic treatment after RP remains undefined. Clinical
trials in this pt population are challenging. Supported by Sanofi
NCT000283062.
4572 General Poster Session (Board #1A), Sun, 8:00 AM-12:00 PM
Intravesical sequential BCG and electromotive mitomycin versus BCG
alone in high risk non-muscle invasive bladder cancer. Presenting Author:
Savino Mauro Di Stasi, Department of Surgery/Urology, Tor Vergata
University, Rome, Italy
Background: In 2006, we reported that intravesical sequential bacillus
Calmette-Guérin (BCG) and electromotive mitomycin in high risk nonmuscle
invasive bladder cancer leads to higher disease-free interval, lower
recurrence and progression, and to improved overall survival and diseasespecific
survival compared with BCG alone. After an additional 6 years of
follow-up, we now report estimated 16-year results. Methods: From 1994
through 2002, we randomly assigned 212 patients with high risk non-
.muscle invasive bladder cancer to 81 mg BCG infused over 120 min once
a week for 6 weeks (n�105) or to 81 mg BCG infused over 120 min once a
week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical
electric current 20 mA for 30 min) once a week as one cycle for three cycles
(n�107). Complete responders underwent maintenance treatment: those
assigned BCG alone had one infusion of 81 mg BCG once a month for 10
months, and those assigned BCG and mitomycin had 40 mg electromotive
mitomycin once a month for 2 months, followed by 81 mg BCG once a
month as one cycle for three cycles. The primary endpoint was disease-free
interval. Analyses were done by intention to treat. Results: Median follow-up
was 121 months (IQR 70.5–163.5). Patients assigned sequential BCG and
electromotive mitomycin had higher disease-free interval than did those
assigned BCG alone (79 months [95% CI 27–139] vs 26 months
[11–113]; difference between groups 53 months [39–67], log-rank
p�0.0002). Patients assigned sequential BCG and electromotive mitomycin
also had lower recurrence (45% [35–55] vs 62% [50–72], difference
between groups 17% [6–28], log-rank p�0.0002); progression (12%
[3–21] vs 28% [17.5–38.5], difference between groups 16% [5–27],
log-rank p�0.003); overall mortality (44% [33–55] vs 59% [43–75],
difference between groups 15% [2–28], log-rank p�0.01); and diseasespecific
mortality (9% [2.5– 15.5] vs 23% [11–34], difference between
groups 14% [4–24], log-rank p�0.0055). Conclusions: In patients with
high risk non-muscle invasive bladder cancer intravesical BCG combined
with electromotive mitomycin provided better results than BCG alone in
terms of higher remission rates and longer remission times.
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