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

4124 General Poster Session (Board #51C), Mon, 8:00 AM-12:00 PM
Prevalence and prognostic significance of FGF receptor 2 (FGFR2) gene
amplification in Caucasian and Korean gastric cancer cohorts. Presenting
Author: Elaine Kilgour, AstraZeneca, Oncology Innovative Medicines,
Macclesfield, United Kingdom
Background: Gastric adenocarcinoma is the 4th most common cancer, and
many patients present with metastatic or recurrent disease. The prognosis
for these patients is poor, with median survival times of 11–12 months.
Hence there is a need for identification of potential new drug targets. We
have determined the prevalence of FGFR2 gene amplification (FGFR2amp)
and its relationship to clinicopathological parameters and survival in
Caucasian (n�408) and Korean (n�356) gastric cancers (GC) and determined
the overlap with HER2 or cMET gene amplification. Methods:
FGFR2, HER2 and cMET gene amplification was assessed by fluorescence
in situ hybridisation in GC tissue microarrays from Caucasian and Korean
surgically resected gastric carcinomas. Gene amplification was defined as a
gene/centromeric probe ratio of �2.0 after measuring at least 50 tumour
cells. Results: 7% (30/408) of Caucasian and 4% (15/356) of Korean GC
showed FGFR2amp, and the incidence was not significantly different
between these cohorts (p�0.092). FGFR2amp was significantly associated
with lymph node status in both cohorts (p�0.0007, multivariate analysis),
and in the Korean cohort with diffuse-type histology, but not with depth of
tumour invasion, age or gender. Patients with FGFR2amp showed significantly
shorter overall survival in both the Caucasian (HR 2.37, 95% CI
1.6–3.5; p�0.0001) and Korean (HR 2.33, 95% CI 1.28–4.25;
p�0.0129) cohorts, by multivariate analysis. There was no overlap
between FGFR2amp and HER2 or cMET amplification in the Korean
cohort, but two of twenty-six FGFR2amp Caucasian gastric tumours also
showed HER2 amplification. Conclusions: This is the first study to demonstrate
FGFR2amp, at a prevalence of 4% and 7%, in two large GC cohorts of
Asian and Caucasian origin and that FGFR2amp is prognostic and significantly
associated with lymph node metastasis. Furthermore, FGFR2amp is
generally mutually exclusive with HER2 and cMET amplifications. Based
on these observations, FGFR2 inhibitors warrant further investigation in the
treatment of FGFR2 amplified GCs.
4126 General Poster Session (Board #51E), Mon, 8:00 AM-12:00 PM
Prevalence of functional tumors in neuroendocrine carcinoma: An analysis
from the NCCN NET database. Presenting Author: Michael A. Choti, The
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University,
Baltimore, MD
Background: Neuroendocrine tumors (NETs) are increasing in incidence
and prevalence. Identification and treatment of specific clinical NET
syndromes are established, yet there is uncertainty regarding the prevalence
of NET with hormone-related symptoms versus nonfunctional tumors.
Methods: The National Comprehensive Cancer Network (NCCN)
created a comprehensive database to characterize patients (pts) treated for
NETs. This database was queried to identify pts presenting to 7 NCCN
institutions with a confirmed NET diagnosis: including carcinoid (cNET),
pancreatic NET (pNET), NET not otherwise specified (NOS), and pheochromocytoma
(PCC) between 2004 and 2010. The primary aim of this analysis
was to describe demographic and clinical characteristics of NET pts by
functional (fxn) status at diagnosis (dx). Results: Among 1244 NET pts,
26% (n�327) had an fxn tumor. Carcinoid syndrome (CS) occurred in 28%
of cNET pts. The most common primary tumor sites among CS pts were
small bowel (69%) and unknown (15%). Prevalence of hormonal syndrome
(HS) among pNET pts was 22%, 24% among NOS pts and 37% among
PCC pts. The majority of CS pts (74%), pNET HS pts (67%), and NOS HS
pts (91%) had distant disease at dx, in contrast to 31% of PCC HS patients.
Among CS pts with a known histologic grade, 91% were well differentiated
(G1). Similarly, 86% of pNET HS and 67% of NOS HS pts with a known
histologic grade had G1 NETs. The most common symptoms at dx among
pts with CS included abdominal cramping (53%), change in bowel habits
(48%), and flushing (40%). Among those tested, 85% of CS pts had a
positive 5-HIAA test at dx. Among pNET HS pts, the most common
symptoms present at dx were abdominal cramping (39%) and change in
bowel habits (46%). The most common symptoms present at dx among
NOS HS pts were abdominal cramping (35%), change in bowel habits
(47%) and flushing (38%). Conclusions: Prevalence of CS in this NCCN
database (28%) was slightly higher than the 10% previously reported in the
literature. In contrast, the prevalence of HS among pNET pts (22%) was
lower than previously reported. Approximately one quarter of cNET pts
without metastatic disease had CS, warranting further analysis as CS most
often occurs in the presence of liver metastasis.
Gastrointestinal (Noncolorectal) Cancer
269s
4125 General Poster Session (Board #51D), Mon, 8:00 AM-12:00 PM
A multi-institutional phase II open-label study of AMG 479 in advanced
carcinoid and pancreatic neuroendocrine tumors. Presenting Author: Matthew
Kulke, Dana-Farber Cancer Institute, Boston, MA
Background: The IGF pathway is thought play an important role in
neuroendocrine tumor progression. We therefore investigated AMG 479, a
human monocolonal antibody against IGF1-R, in patients with metastatic
progressive carcinoid and pancreatic neuroendocrine tumors (NETS).
Methods: This open-label phase II study enrolled patients (�18 yrs) with
metastatic low and intermediate-grade carcinoid and pancreatic NETs. Key
inclusion criteria included evidence of progressive disease (by RECIST)
within 12 months of enrollment, ECOG PS 0-2, and fasting blood sugar
�160mg/dL. Prior treatments were allowed, and concurrent somatostatin
analog therapy was permitted as long as patients remained on a stable
dose. The primary endpoint was objective response rate. Secondary
endpoints included overall survival (OS), progression-free survival (PFS),
and safety. Results: 60 patients (30 carcinoid, 30 pancreatic NET) were
treated with AMG 479 18mg/kg every 3 weeks and 54 patients were
evaluable for response. There were no objective responders by RECIST.
When best response to therapy was evaluated, 10/27 (37%) evaluable
carcinoid patients and 8/26 (31%) evaluable pancreatic NET patients
experienced 1-29% tumor shrinkage, while 17/27 (63%) of the carcinoid
patients and 15/26 (58%) of the pancreatic NET patients appeared to
experience continued tumor growth. Median PFS was 6.3 months (95% CI
4.2-12.6) for the entire cohort; 10.5 months for carcinoid patients and 4.2
months for pancreatic NET patients. The OS rate at 12 months was 70%
(55%-81%) for the entire cohort. Median OS has not been reached.
Treatment related grade 3/4 AEs were rare and consisted of hyperglycemia
(4%), neutropenia (4%), thrombocytopenia (4%) and infusion reaction
(1%). Conclusions: While well-tolerated, single-agent AMG 479 was not
found to result in major tumor responses among patients with metastatic
low-intermediate grade carcinoid or pancreatic NET. Subgroup analysis to
identify characteristics of patients who may have benefited from therapy
with AMG 479 is ongoing.
4127 General Poster Session (Board #51F), Mon, 8:00 AM-12:00 PM
Bevacizumab, pertuzumab, and sandostatin for patients (pts) with advanced
neuroendocrine cancers (NET). Presenting Author: Irfan Firdaus,
Sarah Cannon Research Institute/Oncology Hematology Care, Inc, Cincinnati,
OH
Background: Targeted agents are used to treat well-differentiated NET.
Octreotide binds somatostatin receptors and improves time to progression
(TTP) of carcinoid tumors, and VEGF pathway targeting improves TTP of
pancreatic NET. HER2 overexpression is reported in NET, and pertuzumab
blocks HER2 receptor dimerization. This phase II trial combined bevacizumab,
pertuzumab, and octreotide LAR for pts with advanced NET.
Methods: Pts with advanced well-differentiated NET were enrolled. Pts had
ECOG 0-1, and normal end-organ function, including left ventricular
ejection fraction (LVEF) �50%. Pts received bevacizumab 15 mg/kg IV,
pertuzumab 420 mg IV (following an 840 mg loading dose) day 1 of a 21
day cycle, and octreotide LAR 30 mg IM every 28 days. Primary endpoint
was objective response rate (ORR). Results: Between 6/10 and 4/11, 43 pts
enrolled. 22 M/21 F, med age 62 (33-88), 32 (74%) carcinoid, 11 (26%)
PNET. 26% had prior sandostatin, 72% prior surgery, 19% prior radiation,
23% with � 2 previous systemic therapies. Treatment-related grade 3
toxicities included: hypertension (28%), LVEF dysfunction (9%) (reversible
with trial drug hold), and diarrhea (7%). No grade 4 toxicity was
reported. Median treatment duration was 38 weeks (range: 0 – 76).
Chromogranin A values were elevated in 27 pts; 59% had decreases during
treatment. Seven pts (16%) achieved objective response [CR: 1 carcinoid
(2%), PR: 6 (4 carcinoid, 2 PNET) (14%)]. ORR for carcinoid pts was
15.6%. Median PFS for the entire group was 8.2 months (95% CI: 6.3 –
NA). PFS for carcinoid pts was 8.5 months (95% CI: 6.3 – NA); PFS for
PNET pts was 6.4 months (95% CI: 3.9 – NA). Median OS has not been
reached at 14.3 months followup. Conclusions: The ORR of the combination
of bevacizumab, pertuzumab, and octreotide LAR in NET pts was
encouraging. Particularly the response rate in carcinoid pts appears higher
than historical data, warranting further investigation of this regimen in
these pts.
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