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

246s Gastrointestinal (Noncolorectal) Cancer
4031 Poster Discussion Session (Board #23), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Randomized phase II trial of gemcitabine plus S�1 combination therapy
versus S�1 in advanced biliary tract cancer: Results of the Japan Clinical
Oncology Group study (JCOG0805). Presenting Author: Makoto Ueno,
Kanagawa Cancer Center Hospital, Yokohama, Japan
Background: Gemcitabine plus cisplatin combination (GC) therapy is the
standard therapy for advanced biliary tract cancer (BTC). In previous trials,
gemcitabine plus S-1 combination (GS) therapy and S-1 mono-therapy had
shown considerable efficacy in patients with BTC. The aim of this trial is to
evaluate the efficacy and safety of the two regimens and to determine which
is more promising as a test arm regimen for a subsequent phase III trial.
Methods: Chemotherapy-naive patients with recurrent or unresectable BTC
(gallbladder [GB], intrahepatic biliary duct [IHBD], extrahepatic biliary
duct [EHBD], ampulla of Vater [AV]), an ECOG PS of 0-1,andadequate
organ function were randomly assigned to receive GS (gemcitabine: 1,000
mg/m2 , iv, days 1 and 8; S-1: 60 mg/m2 , p.o., days 1 - 14, every 3 weeks) or
S-1 (80 mg/m2 , p.o., days 1 - 28, every 6 weeks). We assumed that
%1-year survival of one regimen is 30% and that of the other regimen is
more than 40%. To ensure at least 85% probability of correct selection, 98
eligible pts are required. The decision rule was that the regimen with higher
%1-year survival will be considered as more promising regimen. Results:
From February 2009 to April 2010, 101 pts (GB, n�38; IHBD, n�35;
EHBD, n�20; AV, n�8) were randomized (GS, n�51; S-1, n�50). For the
GS arm and S-1 arm, %1-year survivals were 52.9% and 40.0%, the
median survival time were 12.5 and 9.0 months (hazard ratio 0.86 [95%CI
0.54-1.36]; p�0.52), and the median progression-free survival time were
7.1 and 4.2 months (0.44 [0.29-0.67]; p�0.0001). Grade 3/4 hematological
toxicities were more frequent in the GS arm than in the S-1 arm,
(percentage in GS/S-1 arms): neutropenia, 60.8/4.0; leukocytopenia,
29.4/2.0; hemoglobin, 11.8/4.0; and thrombocytopenia, 11.8/4.0; respectively.
Although two treatment-related deaths occurred in the GS arm
(pneumonitis, acute myocardial infarction), other grade 3/4 non-hematological
toxicities were infrequent and reversible in both arms. Conclusions: The
GS arm was superior in %1-year survival to S-1. Here we consider GS to be
more promising as the test arm for a subsequent phase III trial comparing
with GC.
4033 Poster Discussion Session (Board #25), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Observations of hepatocellular carcinoma (HCC) management patterns
from the global HCC bridge study: First characterization of the full study
population. Presenting Author: Joong-Won Park, National Cancer Center,
Goyang, South Korea
Background: HCC is a major health problem across the world. The global
HCC BRIDGE study is the first global, large-scale, observational study to
document the real-world experience of HCC patients from diagnosis to
death. Methods: This longitudinal cohort study (started March 2009)
includes HCC patients newly diagnosed between January 2005 and June
2011 and treated at major medical centers, with data collected retrospectively
and prospectively as recorded in patient charts. Full patient enrollment
is expected at the end of January 2012. Results: At the time of the
first interim analysis (July 2011), 12,442 treated HCC patients were
enrolled at 42 sites in Asia (n�8909, 72% [China: n�6295, 71%; Japan:
n�295, 3%]), Europe (n�2040, 16%) and North America 1493 (n�1493,
12%). Mean age was 57 years; 82% were male. The predominant risk
factor was HBV in Asia (76%) and HCV in Europe (48%), North America
(45%) and Japan (69%). Most patients were diagnosed without surveillance
(Asia, 82%; Europe, 73%; North America, 69%; Japan, 64%). In
Asia, Europe and North America, the predominant BCLC stage at diagnosis
was C (48%, 46%, 46%) followed by A (34%, 28%, 26%). First recorded
treatments in Asia, Europe and North America were resection (31%, 15%,
21%), transplantation (1%, 3%, 1%), TACE (49%, 30%, 36%), other
locoregional therapy (12%, 35%, 23%) and systemic therapy (3%, 10%,
8%). Treatments ever used (2005–2011) in Asia, Europe and North
America were resection (33%, 17%, 24%), transplantation (2%, 6%,
12%), TACE (57%, 35%, 48%), other locoregional therapy (20%, 42%,
37%) and systemic therapy (9%, 20%, 21%). These results will be
updated with data from the full study population (approx. 19,000 patients),
and preliminary survival data will be presented. Conclusions: As the
largest study of its type, in 19,000 patients worldwide, the HCC BRIDGE
study provides valuable insights into global HCC disease characteristics
and patient management. Based on prior analyses, differences in risk
factors among regions confirm well-known trends, while other observed
differences (e.g., treatment variations) may be related to country- and
site-specific practices and patient characteristics.
4032 Poster Discussion Session (Board #24), Mon, 1:15 PM-5:15 PM and
4:45 PM-5:45 PM
Gemcitabine and oxaliplatin (GEMOX) alone or in combination with
cetuximab as first-line treatment for advanced biliary cancer: Final analysis
of a randomized phase II trial (BINGO). Presenting Author: David Malka,
Institut Gustave Roussy, Villejuif, France
Background: Gemcitabine-platinum chemotherapy (CTx) regimens are widely
accepted as first-line standard of care for patients (pts) with advanced
biliary cancers (ABC). EGFR overexpression has been observed in ABC,
suggesting that the combination with anti-EGFR monoclonal antibodies
may be appropriate. Methods: Patients with ABC, WHO performance status
(PS) 0-1, and without prior palliative CTx were eligible for this international,
open-label, two-stage, non-comparative, randomized phase II trial.
Patients received GEMOX (gemcitabine, 1 g/m² [10 mg/m²/min] at day [D]1
� oxaliplatin, 100 mg/m² at D2, arm A) or GEMOX � cetuximab (500
mg/m² at D1 or 2, arm B), every 2 weeks. The primary endpoint was crude
4-month progression-free survival (PFS) rate (H0, �40%; H1, �60%;
planned sample size, 100 pts, increased to 150 pts by amendment to allow
subgroup analyses). Secondary endpoints were objective response rate
(ORR), disease control rate (DCR), PFS, overall survival (OS), and toxicity
(NCI-CTC v3.0). Exploratory endpoints included early metabolic response
as assessed by PET at 1 month, and tumor KRAS mutational analysis.
Results: From Oct. 2007 to Dec. 2009, we enrolled 150 pts (median age,
62 years; male, 57%; metastatic, 79%; cholangiocarcinoma, 84%; median
follow-up, 30 months) (Table). Conclusions: GEMOX-cetuximab regimen
was well tolerated and met its primary endpoint (4-month PFS
�60%). However, median PFS and OS were similar in both arms.
Exploratory analyses (e.g., KRAS tumor status) are underway to identify pt
subgroups deriving benefit from the addition of cetuximab to CTx.
Arm A Arm B
Cycles (median) (n) 10 10
Toxicity (%) 1
Peripheral neuropathy 2
46 49
Neutropenia 16 22
Fatigue 13 17
Thrombocytopenia 19 11
Gastrointestinal 15 13
Allergy/hypersensitivity 1 8
Rash 0 7
Efficacy [95% CI]
ORR (%) 3
29 [18-40] 23 [13-33]
DCR (%) 3
77 [67-88] 87 [79-95]
4-month PFS (%) 53 [41-64] 63 [52-74]
PFS (median, months) 5.3 [3.7-6.6] 6.0 [5.0-7.4]
OS (median, months) 12.4 [8.6-16.0] 11.0 [8.9-13.7]
1 Grade 3-4, NCI-CTC v3.0.
2 Grade 2-3, Modified Levi’s scale.
3 In 131 evaluable pts.
4034 General Poster Session (Board #40A), Mon, 8:00 AM-12:00 PM
Final results of a phase I/II study in patients with pancreatic cancer,
malignant melanoma, and colorectal carcinoma with trabedersen. Presenting
Author: Helmut Oettle, Universitätsmedizin Berlin Charite, Campus
Virchow-Klinikum, Berlin, Germany
Background: TGF-�2 overexpression in solid tumors triggers key cancer
pathomechanisms, i.e. suppression of antitumor immune responses system
and metastasis. Trabedersen specifically inhibits TGF-�2 expression.
In the clinical Phase I/II study we evaluate MTD, safety, pharmakokinetics
(PK), and efficacy of i.v. trabedersen in patients with advanced tumors.
Methods: A total of 61 patients with pancreatic cancer (PancCa, n�37),
malignant melanoma (MM, n�19), or colorectal carcinoma (n�5) were
treated with i.v. trabedersen as 2nd to 4th-line therapy with escalating doses
in 2 treatment schedules. (1st schedule: 7d on, 7d off; 2nd schedule: 4d on,
10d off; up to 10 cycles). Within the 1st schedule, the MTD was established
at 160 mg/m2 /d. In the 2nd schedule dose-escalation was stopped before
reaching MTD. In the Phase II-part of the study further PancCa and MM
patients were treated with 140 mg/m2 /d. For assessment of PK parameters,
plasma time profiles were analyzed for trabedersen and its n-1 to n-5
metabolites by non-compartimental analysis. Results: Trabedersen was safe
and well-tolerated. The only expected adverse reaction identified is
non-serious and transient thrombocytopenia. Only 2 SAEs (gastrointestinal
hemorrhage und pyrexia) were considered as possibly related to study
medication. Further clinical development will focus on PancCa patients
receiving 140 mg/m2 /d trabedersen as 2nd-line treatment. Survival analysis
of these patients revealed a mOS of 13.4 months (n�9; 95% CI: 2.2,
39.7). One PanCa patient had a complete response of liver metastases and
is still alive after 75 months. Promising efficacy data were also seen in MM
patients enrolled into the last cohort (140 mg/m2 /day) with a current mOS
of 9.3 months (n�14; 95% CI: 6.5, 12.2). PK analyses showed for both
treatment schedules that exposure to trabedersen was in the expected
range for all doses and half-life of trabedersen (1.12 to 2.08 hrs) as well as
clearance (2.22-4.37 L/h*m2 ) were independent of dose. Conclusions:
Trabedersen showed excellent safety and encouraging survival results in
the Phase I/II clinical study. A randomized, active-controlled study in 2nd line stage IV PanCa patients is in preparation.
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