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

248s Gastrointestinal (Noncolorectal) Cancer
4039 General Poster Session (Board #40F), Mon, 8:00 AM-12:00 PM
Baseline albumin (b-alb) as a potential predictive biomarker for the efficacy
of bevacizumab (B) therapy (tx) in patients (pts) with advanced pancreas
cancer (APCA): A comparative analysis. Presenting Author: Ludmila Katherine
Martin, The Ohio State University Medical Center, Columbus, OH
Background: Phase III studies of B in unselected pts with APCA have
demonstrated no improvement in outcome. Recent data suggest certain
subsets of APCA patients may benefit from B. Lower b- alb results in a
15-20% increased rate of B clearance that may decrease exposure to B.
The resulting clinical implications are not well understood. We evaluated
the potential predictive and prognostic role of b-alb in pts with APCA
receiving gemcitabine (G)-based tx with or without B. Methods: Relevant
data were collected from 3 prospective phase II studies of G-based tx. Pts
were grouped according to exposure to B (Gr 1) or no B (Gr 2) and by b-alb
� 3.4 g/dL (� LLN) or � 3.4 g/dL (�LLN). Univariate and multivariate
analyses of clinical outcome (OS, TTP) were conducted for each group and
all pts. Results: 100 pts (46M, 54F) with median age 63 (range 28-82)
were included. 94% had stage IV. Median b-alb was similar in both groups.
Clinical outcomes by alb are outlined in the table. In Gr 1 but not Gr 2,
b-alb � 3.4 g/dL was significantly associated with improved OS and TTP.
For pts with b-alb �3.4 g/dL, maintenance of alb �3.4 g/dL throughout tx
was significantly associated with improved survival in Gr 1 but not Gr 2.
Multivariate analysis revealed significant association between alb � 3.4
and OS regardless of B status (p�0.004) although this was strongly
influenced by the survival differential in Gr 1. Conclusions: APCA pts with
b-alb � 3.4 g/dL appear to derive significant benefit from B and this benefit
is most pronounced in pts who maintain alb � 3.4 g/dL throughout B tx.
This finding was not observed in pts treated without B. b-alb � 3.4 g/dL
including maintenance of alb � 3.4 g/dL during B tx may predict for
improved efficacy of B in APCA. These findings require further investigation
in larger prospective trials.
Clinical outcome according to alb.
Group 1 (N�42) Group 2 (N�58)
b-alb � 3.4 g/dL b-alb � 3.4 g/dL p b-alb � 3.4 g/dL b-alb � 3.4 g/dL p
(N�28)
(N�14)
(N�43)
(N�15)
mOS (m) 10.7 3.1 0.00175 7.3 5.4 0.22
mTTP (m) 7.7 2.7 0.009 3.9 2.8 0.76
alb � 3.4 w/tx alb 2to � 3.4 w/tx p alb�3.4 w/tx alb 2to � 3.4 w/tx p
(N�9)
(N�19)
(N�8)
(N�29)
mOS (m) 20.1 8.6 0.003 8.9 5.9 0.63
4041 General Poster Session (Board #40H), Mon, 8:00 AM-12:00 PM
Development of the SP120 rabbit monoclonal antibody for determining
hENT1 status and predicting response to gemcitabine in pancreatic ductal
adenocarcinoma. Presenting Author: Stefan Hubert Boeck, Department of
Hematology and Oncology, Klinikum Grosshadern and Comprehensive
Cancer Center, LMU Munich, Munich, Germany
Background: Human equilibrative nucleoside transporter 1 (hENT1) is the
primary membrane channel through which gemcitabine (Gem) enters
pancreatic tumor cells. Patients whose tumors have low expression of
hENT1 may derive little benefit from Gem therapy. Methods: We have
developed and analytically validated a rabbit monoclonal antibody, SP120,
immunohistochemistry (IHC) in vitro diagnostic (IVD) assay, used on the
VENTANA BenchMark ULTRA automated slide staining platform, for
assessing hENT1 expression in pancreatic adenocarcinoma. Results: SP120
was shown to be sensitive and specific for membrane expression of hENT1
with variable expression demonstrated across a panel of primary pancreatic
adenocarcinoma samples. Using retrospectively collected primary tumor
samples (n � 201) from a randomized controlled clinical adjuvant trial
(RTOG 97-04), we developed and verified a hENT1 scoring algorithm and
cut-off for identifying patients least likely to benefit from Gem (hENT1low).
We confirmed the predictive value of the hENT1 assay by showing
there was no association with clinical outcome in the 5FU-treated control
group. The distribution of hENT1 expression was similar between these
samples and an independent set of 130 pancreatic adenocarcinoma
specimens from the AIO-PK0104 study (77 were confirmed metastatic
biopsies). Importantly, 100% concordance in hENT1 status (high vs. low)
was demonstrated between 16 primary tumors and paired, contemporaneous
metastatic lesions. Overall, using this cut-off, approximately two thirds
of pancreatic tumors displayed low-hENT1 expression across the different
data sets (n � 363). Conclusions: The hENT1 IHC IVD has been developed
and is being used in a pivotal trial of a novel lipid-conjugated Gem
(CO-101, which enters tumor cells independently of hENT1), vs. Gem in
hENT1-low pancreatic cancer patients (NCT01124786). This study is the
first prospective test of the hypothesis that gemcitabine is not active in
tumors with low hENT1 expression.
4040 General Poster Session (Board #40G), Mon, 8:00 AM-12:00 PM
Antitumor activity of nab-paclitaxel and gemcitabine in resectable pancreatic
cancer. Presenting Author: Rafael Alvarez-Gallego, Centro Integral
Oncológico Clara Campal, Madrid, Spain
Background: Nab-paclitaxel in combination with gemcitabine has shown
interesting clinical activity in patients with advanced pancreatic cancer
(PDA) likely related to its ability to eliminate pancreas cancer stroma. In
this study we explore clinical and pathological effects of the combination in
patients with operable PDA. Methods: Patients with resectable o borderline
resectable pancreatic cancer were treated with gemcitabine(1000mg/m2
days 1, 8 and 15) and nab-paclitaxel(125mg/m2 days 1, 8 and 15) for two
cycles prior to surgery. Response was assessed by FDG-PET, CA199 levels
and elastography, an EUS-based non invasive assessment of tumor stroma.
Results: 16 patients were included into the study. 2 patients (12.5%)
showed a progression disease (both with hepatic metastases) and were not
operated. Median value for PET SUVmax decreased from 7,1 pre-treatment
to 4,6 post-treatment(p�0.004), including 7(50%) of patients with a
partial metabolic response and the mean CA199 decreased from 2654 to
52(p�0.02) with 43% patients having a more that 75 % decrement in
tumor marker. The elastography ratio value diminished from 36 pretreatment
to 18 post-treatment(p�0.003) and correlated with improvement
in SUVmax(p�0.04) and CA199 response(p�0,07). Grade 3-4
toxicities were neutropenia in 18% (none febrile neutropenia), thrombocytopenia
in 12.5 and 6.2% transaminase elevation. So far 9 patients have
been operated and in 8(89%) a complete resection (R0) was achieved. 1
patient had a complete pathological response and 4 patients had near
complete responses with only a few(� 5%) residual tumor. In-depth
analysis of stromal composition after treatment showed, compared to a
series of 10 cases untreated and treated with conventional chemoradiation,
decreased myofibroblast content, increase vessel density and distorted
collagen fibers. Conclusions: Neoadjuvant treatment with gemcitabine plus
nab-paclitaxel is feasible and results in significant clinical activity. Noninvasive
elastography appears and attractive method to monitor tumor
response. The rate of pathological responses and R0 resections in substantial
for this setting. Biological studies of resected specimens show unique
effects in tumor stroma.
4042 General Poster Session (Board #41A), Mon, 8:00 AM-12:00 PM
A phase III trial of ganitumab (GAN, AMG 479) with gemcitabine (G) as
first-line treatment (tx) in patients (pts) with metastatic pancreatic cancer
(MPC): An analysis of safety from the GAMMA trial (GEM and AMG 479 in
Metastatic Adenocarcinoma of the Pancreas). Presenting Author: Charles
S. Fuchs, Dana-Farber Cancer Institute, Boston, MA
Background: GAN is an investigational, fully human, monoclonal antibody
inhibitor of IGF1R. GAMMA is assessing the safety and efficacy of GAN plus
G as first-line tx in MPC pts (ClinicalTrials.gov ID: NCT01231347).
Methods: This is an ongoing, global, phase III, double-blind study. Pts are
randomized 2:2:1 to receive placebo, GAN 12 mg/kg, or GAN 20 mg/kg (IV;
days 1 and 15 Q28D) with G 1000 mg/m2 (IV; days 1, 8, and 15 Q28D).
The planned sample size is 825. Primary endpoint: overall survival. Key
secondary endpoints: progression-free survival, 1-year survival rate, patientreported
outcomes, and safety. This study includes multiple planned safety
analyses conducted by an independent Data Monitoring Committee (DMC).
The current predefined safety analyses occurred when 150pts received � 1
cycle of tx. Results: As of Sep 16, 2011, 207 pts are included in this
aggregate analysis: 50% male; median age, 63 yrs (range 36-83); ECOG
PS 0/1, 50%/50%. Of the 207 pts, 204 pts received study tx, and 61 pts
ended study tx. Most frequent adverse events (AE) are shown (table). Ten
pts (5%) died during or within 30 days of the end of tx. Seven events were
attributed to or associated with disease progression. One event of cardiac
failure was reported to be possibly tx related. Pulmonary embolism was
suspected but not confirmed. Conclusions: The GAMMA study continues
per protocol. The only grade 3/4 AE occurring in more than 5% of patients
to date is neutropenia.
Any grade AE occurring in > 15% of pts or higher grade AE in > 3% of ptsa .
Any grade-n(%)
CTCAE v3.0
Grade 3/4-n(%)
CTCAE v3.0
AE, MedDRA terms
Thrombocytopenia b
Neutropenia
79 (39) 8 (4)
c
72 (35) 47 (23)
Nausea 69 (34) 4 (2)
Fatigue 56 (27) 9 (4)
Decreased appetite 45 (22) 2 (1)
Vomiting 38 (19) 4 (2)
Pyrexia 36 (18) 0 (0)
Diarrhea 35 (17) 1 (0)
Leukopenia 34 (17) 7 (3)
Alanine aminotransferase increased 28 (14) 9 (4)
Hyperglycemia 27 (13) 9 (4)
Aspartate aminotransferase increased 23 (11) 7 (3)
Asthenia 21 (10) 6 (3)
a Analysis includes all 3 tx arms and excludes 3 pts who did not receive any tx; b Includes
platelets decreased; c Includes neutrophils decreased.
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