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

262s Gastrointestinal (Noncolorectal) Cancer
4095^ General Poster Session (Board #47F), Mon, 8:00 AM-12:00 PM
Two-year follow-up of a phase II study on catumaxomab as part of a
multimodal approach in primarily resectable gastric cancer. Presenting
Author: Carsten Bokemeyer, Department of Oncology/Hematology, University
Hospital Hamburg, Hamburg, Germany
Background: Perioperative chemotherapy (CT) has demonstrated as survival
benefit in locally advanced gastric cancer (GC) in randomized trials.
However, the overall cure rate is 30-40% and a significant number of
patients are not able to receive the postoperative part of their CT regimen.
In Europe, the trifunctional antibody catumaxomab is approved for the
treatment of malignant ascites based on a pivotal trial which also included
GC patients. A new multimodal approach combining neoadjuvant CT,
followed by gastrectomy and intraperitoneal (i.p.) immunotherapy with
catumaxomab was assessed in a single-arm multicenter phase II study. We
here report 2-year follow-up data. Methods: GC pts (T2/T3/T4, N�/–, M0)
received 3 cycles of neoadjuvant fluoropyrimidin/platinum-based CT followed
by ´en-bloc´ R0-gastrectomy. Catumaxomab was administered i.p. as
intraoperative bolus (10 �g) followed by 4 consecutive 3-hour infusions of
10-150 �g. Primary safety endpoint was the rate of predefined postoperative
complications observed during 30 days after surgery. Key efficacy
endpoints included disease-free (DFS) and overall survival (OS). Results:
The original study data presented at the WCGC in 2011 (Schuhmacher et
al.,Ann Oncol (2011) 22(suppl. 5)) showed that the primary endpoint was
met and the described application regimen is safe. At time of surgery,
27.8% of patients were stage I, 27,8% of patients were stage II, 22,3% of
patients were stage III and 14,8% of patients were stage IV as assessed
according to pTNM measures. At 24 months 39/54 (safety analysis set)
patients were still alife,14/54 were dead, (one patient lost to follow-up),
24/37 had no progression, only 13/37 patients relapsed (for 2 patients
disease status was not recorded). At the 2 year cut off DFS was 56.4%
(95% CI: 41–69%), OS was 75% (95% CI: 60–85%). Conclusions:
Catumaxomab as part of a multimodal therapy in primarily resectable GC is
a feasible option. The 2-year follow up efficacy results show promising data
for DFS and OS in a cohort of locally advanced gastric cancer pts.
4097 General Poster Session (Board #47H), Mon, 8:00 AM-12:00 PM
Sequential chemotherapy with dose-dense docetaxel, cisplatin, folinic acid
and 5-fluorouracil (TCF-dd) followed by oxaliplatin, folinic acid, 5-fluorouracil,
and irinotecan (COFFI) in locally advanced or metastatic gastric
cancer (MGC). Presenting Author: Gianluca Tomasello, Istituti Ospitalieri,
Cremona, Italy
Background: MGC is a chemosensitive tumour. According to the Norton-
Simon hypothesis, a reduction of tumor burden could best be achieved by
shortening the interval between the cycles, and the resistance might be
overcome by switching from initial chemotherapy to a new, non crossresistant
one. We previously reported on the high efficacy of a new strategy
using 2 sequential, non cross-resistant chemotherapy regimens in MGC
(Cancer Chemother Pharmacol 11 Jan; 67 (1): 41-8). Aim of this study is to
evaluate this therapeutic approach in a larger case series. Methods: 43
patients (pts) treated at our centre from November 04 to April 11 were
included. All pts were chemo-naïve and received 4 cycles of TCF-dd (see
reference above for doses) every 2 weeks. Subsequently and irrespective of
their response, they received 4 cycles of COFFI (see reference above ) every
2 weeks. In both regimens pegfilgrastim 6 mg sc on day 3 was included.
Results: Median age: 63; 74% male. PS 0-1. After the first regimen
(TCF-dd) 43 pts were evaluable for response.We registered 3 CR, 27 PR, 7
SD, 5 PD and 1 not evaluable for an ORR at ITT of 70% (95% CI, 58-85).
All pts proceeded to the second regimen (COFFI) and 40 pts were evaluable
for response. The 3 CR observed after TCF-dd were maintained. Among the
27 pts with PR after TCF-dd, 2 achieved CR, 14 improved the response, 6
maintained PR, 3 progressed. Among the 7 pts with SD after TCF-dd, 1
achieved CR, 3 achieved PR, 2 progressed and 1 is not valuable. Among the
5 pts with PD after TCF-dd, 1 achieved CR, 4 achieved RP. After COFFI we
observed 5 CR, 21 PR, 9 SD and 5 PD. The ORR in the 40 pts was 60%
(95% CI, 50-80). Considering both regimen ORR was 93%. mTTP was
12.1 months (95% CI, 8,1-16,2). mOS was 16.1 months (95% CI,
12.7-21.6). At Dec ’11, 4 out of 8 pts who achieved CR are alive and
disease free. Most frequent G3-4 toxicities were: astenia (32%), neutropenia
(35%), anemia (14%), neurotoxicity (21%). Conclusions: The study
confirms that a sequential dose-dense strategy using TCF-dd followed by
COFFI is feasible and highly effective and deserves to be tested in a
randomized study which is on going.
4096 General Poster Session (Board #47G), Mon, 8:00 AM-12:00 PM
A phase II study of capecitabine-oxaliplatin and cetuximab in patients
(pts) with advanced/metastatic gastric cancer (G) or gastroesophageal
junction (GEJ) adenocarcinoma. Presenting Author: Syma Iqbal, University
of Southern California Norris Comprehensive Cancer Center, Los Angeles,
CA
Background: There have been limited advances in the treatment (tx) of pts
with metastatic G or GEJ adenocarcinoma. The combination of fluroropyrimidines
and platinums are standard regimens for this disease. The epidermal
growth factor receptor pathway has been identified as a target and KRAS
mutations are rare. Methods: The primary objective was to assess the
proportion of pts with progression within 4 months. Secondary objectives
include response (RR), progression free survival (PFS) overall survival (OS),
toxicity and molecular correlates. A two-stage Simon phase II design was
used to distinguish between a 30% vs. 50% 4 month PFS; with analysis
planned at 27 and 53 pts. Eligible pts were chemonaive, metastatic/
unresectable with measurable disease. Pts received capecitabine 850
mg/m2 BID D1-14, oxaliplatin 130 mg/m2 IV D1, cetuximab 400 mg/m2
(load) then 250 mg/m2 IV D1, 8, 15, q21 days. Blood and tissue were
analyzed for genes in the DNA repair and EGFR pathways. Results: 61 pts
were accrued, 2 GEJ and 59 G; 42 male, 19 female; median age 56 years
(28-86); 54 pts were evaluable. The 4 month PFS rate 61% (95%CI
47-73%), PFS 5.4 months (95% CI 3.5-6.7); RR 50% (95%CI: 36-64%),
1 (1.9%) complete, 26 (48.1%) partial, 22 (40.7%) stable disease; 2
(3.7%) pts became resectable; median OS 14.9 months (95% CI 8.8-
22.2) with median follow-up of 21.8 months. 65% (39/60) of pts had
grade 3 (36 pts) or 4 (3 pts) toxicity; most common, anorexia (13.3%),
diarrhea (13.3%), fatigue (13.3%), nausea (15%), vomiting (15%); grade
3 hand/foot (5.3%), acneiform rash (3.3%). SNP’s in LRIG4, (regulator of
EGF signaling) and PAI1 (tumor angiogenesis, cell proliferation, migration
and adhesion) were significantly associated with RR (67% G/G vs 17% A/A
,p�0.044) and PFS (5.8 months 5G/4G vs 3.4 months 5G/5G, p�0.017)
respectively. Conclusions: XELOX and cetuximab has promising activity,
comparable to existing regimens. Novel SNP’s were identified correlating
with RR and PFS which may allow for optimization of pt selection.
4098 General Poster Session (Board #48A), Mon, 8:00 AM-12:00 PM
Lenalidomide for second-line treatment of advanced hepatocellular cancer
(HCC): A Brown University Oncology Group phase II study. Presenting
Author: Howard Safran, Brown University Oncology Group, Providence, RI
Background: Lenalidomide inhibits fibroblast growth factor (FGF), vascular
endothelial growth factor (VEGF) and multiple tumor growth pathways.
There is no standard of care for patients who progress after sorafenib.
Therefore, we performed a phase II study to determine the activity of
lenalidomide in second-line HCC therapy. Methods: Patients with advanced
HCC who progressed on or were intolerant to sorafenib were eligible. Prior
chemoembolization, RFA, or surgery were allowed. Eligibility criteria also
included bilirubin �4 mg/dL, AST and ALT �5 times upper limit of normal,
ECOG performance status 0-2, platelet count �60,000/mm3 , absolute
neutrophil count �1000/mm3 , and creatinine �2mg/dL. Patients were
treated with lenalidomide 25mg orally days 1-21 of a 28 day cycle until
disease progression or unacceptable toxicities. The planned original
sample size was 25 patients but when early activity was demonstrated the
study was expanded to 40 patients. Results: The study has completed
accrual of 40 patients. The median age was 60.5 years (17-88 years).
Nineteen patients were Child-Pugh A, 16 patients were B, and 5 patients
were C. Twenty four patients had extrahepatic disease. Preliminary data is
available on the first 37 patients. One patient had grade 4 neutropenia.
Grade 3 toxicities included ANC (n�2), fatigue (n�4), rash (n�2), arthritis
(n�1), diarrhea (n�1), dehydration (n�2). One patient developed variceal
bleeding which precipitated encephalopathy and death. Of the 32 patients
with elevated baseline AFP, nine (28%) had a �50% reduction including
one patient with a reduction in AFP from 56,900ng/ml to 5 ng/ml. Six of
the first 37 patients (16%) had a radiographic partial response. Two
patients achieved a complete response and have not progressed at 36 and
32 months. Conclusions: Lenalidomide can be administered to patients
with advanced HCC and significant hepatic dysfunction. Promising, and in
a small percentage of patients, dramatic and durable activity has been
demonstrated. Investigations are underway to explore the mechanism of
action of lenalidomide in HCC.
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