Neuroendocrine & endocrine tumours and CUP

Chair(s)

K. Oeberg (Uppsala, Sweden)B. Skogseid (Uppsala, Sweden)P. Ruszniewski (Clichy, France)

Session
Type

Poster Discussion session

Details

ESMO 2014, 29.09.2014, 12:45 - 13:45, Alicante

1134PD - Treatment satisfaction, symptom control, and quality of life (QoL) with
lanreotide autogel (LAN) in neuroendocrine tumour (NET) patients with carcinoid
syndrome (CS): results from the SymNET study
P. Ruszniewski (Clichy, France)M. Caplin (London, United Kingdom)J. W. Valle (Manchester, United Kingdom)
C. Lombard-Bohas (Lyon, France)G. Poston (Liverpool, United Kingdom)
P. Perros (Newcastle-upon-Tyne, United Kingdom)L. Holubec (Pilsen, Czech Republic)G. Delle Fave (Rome, Italy)
D. Smith (Bordeaux, France)P. Niccoli (Marseille, France)P. Maisonobe (Boulogne-Billancourt, France)
P. Atlan (Boulogne-Billancourt, France)
Aim
CS associated with NETs can have a negative impact on patients' QoL. Here, QoL data
are evaluated from the SymNET study.
Methods
SymNET was a large observational study of NET patients with a history of CS-related
diarrhoea treated with LAN for >3 mo (NCT01234168). Patient-reported outcomes were
assessed at a routine clinic visit. Primary endpoint was patient satisfaction with diarrhoea
control (PSD). Symptoms were evaluated using medical records. QoL was assessed
using the EORTC QLQ-C30 and QLQ-GI.NET21 questionnaires, which assess functional
dimensions (QLQ-C30; higher scores = better QoL) and symptoms (QLQ-C30 and
QLQ-GI.NET21; lower scores = better QoL). Overall QoL was evaluated according to
satisfaction with CS symptom control.
Results
Among 273 patients enrolled, 76% [95% CI: 70, 81%] were completely or rather
satisfied with diarrhoea control. There was a clinically significant reduction in stool number
and statistically significant improvements in urgency, leakage, and associated pain since
LAN initiation. Scores for the QLQ-C30 global health status were high (mean [SD] 65.5
[22.1], median [range] 66.7 [0100]), while scores for the QLQ-GI.NET21 endocrine and
gastrointestinal subscales were low (endocrine, mean [SD] 19.4 [21.3], median [range]
11.1 [0100]; gastrointestinal, mean [SD] 22.9 [17.8], median [range] 20.0 [087]).
Patients who expressed a high PSD scored well on their overall rating of QoL (Table); in
total, 70% of patients who were rather or completely satisfied had good, very good, or
excellent QoL.
QoL according to PSD
n (%)
Rather' or
completely
satisfied(n = 200)
Overall QoL

Neither satisfied nor Rather or

dissatisfied(n = 46) completely
dissatisfied(n = 18)

Very poor, poor, 28 (14)

or slightly poor

12 (26)

5 (28)

Neither poor nor 32 (16)

good

12 (26)

6 (33)

Good, very
good, or
excellent

22 (48)

7 (39)

140 (70)

Conclusions
In a real world setting, CS symptom control with LAN treatment translates into favourable
levels of satisfaction among NET patients. Higher satisfaction levels were consistent with
higher global health QoL scores. Further analyses are ongoing to evaluate factors
associated with better QoL.
Disclosure
P. Ruszniewski: Ipsen: Consultant/advisory role; honoraria; research funding; partner is
Ipsen employee. Novartis: honoraria and research funding; M. Caplin: IPSEN: honoraria
for consultant/advisory role. NOVARTIS: Consulting fee, Advisory Committees or Review
Panels; LEXICON: Consulting fee, Advisory Committees or Review Panel; J.W. Valle:
Ipsen: consulting, honoraria; P. Niccoli: Ipsen: consulting and honoraria; P. Maisonobe:
Ipsen: Employment and salary; P. Atlan: Ipsen: Employment and salary. All other authors
have declared no conflicts of interest.

1135PD - Quality of life (QoL) associated with lanreotide autogel (LAN) treatment
for carcinoid syndrome (CS) in gastroenteropancreatic neuroendocrine tumour
(GEPNET) patients: Results of the ELECT study
E. Gomez-Panzani (Boulogne-Billancourt, France)A. I. Vinik (Norfolk, United States of America)
E. M. Wolin (Los Angeles, United States of America)H. Audry (Boulogne-Billancourt, France)
Aim
QoL is an important consideration for CS treatment. This analysis evaluated QoL in
GEP-NET patients treated for CS in the ELECT study.
Methods
ELECT was a 16-week, randomised, double-blind (DB) phase III study (NCT00774930).
Patients with GEP-NETs and a history of CS were treated with LAN 120mg (n = 59) or
placebo (n = 56) every 4 weeks. It was followed by 32-week and 2-year open-label
extensions (OLEs). The primary endpoint was % of days of rescue medication use (SC
octreotide) during DB study. Safety evaluations focused on adverse events (AEs). QoL
was assessed using the EORTC QLQ-C30 and the EORTC QLQ-GI.NET21. Scores for
global health status score (QLQ-C30) and endocrine and gastrointestinal subscales
(QLQ-GI.NET21) were secondary endpoints; other scores were exploratory.
Results
Mean [95% CI] % of days of rescue medication use was significantly lower with LAN (34%
[25, 42%]) than placebo (49% [40, 57%]); difference 15% [27, 3%], p = 0.02.
Treatment-related AEs occurred in 15 (26%) LAN vs. 11 (19%) placebo patients: most
common AEs were gastrointestinal. The global health status score (QLQ-C30) remained
similar after 12 weeks of DB treatment with LAN and placebo. Treatment differences in
endocrine and gastrointestinal subscale scores are shown in the table. For all functional

scales of the QLQ-C30, scores remained stable/slightly improved in the LAN group, while
there were small deteriorations in the placebo group; however CIs were wide. For the
other subscales of the QLQ-GI.NET21, changes in scores were similar in both treatment
groups.
Conclusions
LAN 120mg treatment for CS symptoms was not associated with a deterioration in QoL
in GEP-NET patients. In fact, despite the relatively short duration of the study, there was
evidence of initial improvements in some aspects of QoL. Results of QoL scores in OLE
may provides more information. Table: Effect of LAN on QoL secondary endpoints.
Values are mean (SD) unless otherwise stated. P-value tested at a significance level of
0.05. A hierarchical testing procedure was applied for secondary endpoints. Data shown
are for the transformed scores, which can range from 0 to 100. A higher transformed
score for global health status represents a better QoL. A higher transformed score for
Endocrine and GI symptoms represents a higher level of symptomatology/problems
Lanreotide Placebo
Autogel

LS mean treatment difference

in change from baseline [95%
CI]

p-value

Baseline

59.89
62.58
(20.15) [n = (20.28) [n
59]
= 55]

4.05 [2.09, 10.20]

0.1931

Week 12

64.93
61.19
(19.37) [n = (18.07) [n
48]
= 35]

4.05 [2.09, 10.20]

0.1931

Baseline

25.89
33.54
(22.83) [n = (23.92) [n
59]
= 53]

7.04 [14.80, 0.73]

0.0750

Week 12

18.06
29.84
(20.06) [n = (22.51) [n
48]
= 35]

7.04 [14.80, 0.73]

0.0750

Baseline

22.40
24.84
(16.95) [n = (20.09) [n
59]
= 53]

4.68 [9.63, 0.26]

0.0632

Week 12

17.64
23.62
(14.32) [n = (15.45) [n
48]
= 35]

4.68 [9.63, 0.26]

0.0632

QLQ-C30 Global
health status/QoL

QLQ-GI.NET21
Endocrine symptoms

QLQ-GI.NET21
Gastrointestinal
symptoms

Disclosure
E. Gomez-Panzani: Ipsen: employee; A.I. Vinik: Ipsen: Research grant, advisory board
member; E.M. Wolin: Research grant from Ipsen. Advisory board member for Ipsen,

Novartis and Celgene; H. Audry: Received consulting fee (contract statistician) from Ipsen.

1136PD - Quality of life (QoL) with lanreotide autogel (LAN) vs. placebo in patients
with enteropancreatic neuroendocrine tumours (EP-NETs): results from the
CLARINET phase III study
P. Ruszniewski (Clichy, France)M. Caplin (London, United Kingdom)M. Pavel (Berlin, Germany)
J. wika (Olsztyn, Poland)A. Phan (Houston, United States of America)M. Raderer (Vienna, Austria)
E. Sedlackova (Prague, Czech Republic)G. Cadiot (Reims, France)L. Wall (Edinburgh, United Kingdom)
G. Rindi (Rome, Italy)A. Langley (Les Ulis, France)J. Blumberg (Les Ulis, France)
E. Gomez-Panzani (Les Ulis, France)
Aim
QoL in patients with gastroenteropancreatic-NETs can be affected by the symptom
burden, but also treatment efficacy and safety. To better evaluate this, the EORTC
developed a NET-specific QoL questionnaire (QLQ-GI.NET21), to be used in combination
with its more generic questionnaire, EORTC QLQ-C30. Here, we examine the impact of
LAN vs. placebo on QoL from the CLARINET study.
Methods
CLARINET was a 96-week randomized double-blind phase III study, in which patients with
well/moderately differentiated, non-functioning EP-NETs were treated with LAN 120mg
(n = 101) or placebo (n = 103) deep SC injections every 4 weeks (NCT00353496). The
primary endpoint was progression-free survival (PFS). Safety was a key secondary
endpoint. QoL (also a secondary endpoint) was assessed at each study visit using the
EORTC QLQ-C30 and the EORTC QLQ-GI.NET21.
Results
LAN significantly prolonged PFS vs. placebo (stratified log rank, p = 0.0002; hazard ratio
0.47 [95% CI: 0.30, 0.73]). Treatment-related adverse events (AEs) occurred in 50% of
patients in the LAN group vs. 28% in the placebo group. Gastrointestinal disorders were
the most common AEs (37% vs. 19%). The QLQ-C30 global health status scores and the
QLQ-GI.NET21 endocrine and gastrointestinal subscale scores were similar in the two
treatment groups at baseline and throughout treatment, though inter-individual variation
was high (Table). Results for the other subscale scores of the QLQ-C30 and
QLQ-GI.NET21 questionnaires were also similar between LAN and placebo.
Conclusions
Overall, patients on LAN 120mg had a significantly improved PFS and a good
safety/tolerability profile that did not compromise patients' QoL vs. placebo. Further
analyses are ongoing to evaluate QoL based on patient characteristics and treatment
response. Table: Effect of LAN treatment on patients' QoL.
Values are mean (SD); LVA, last post-baseline value available Data shown are for the
transformed scores, which can range from 0 to 100. A higher transformed score for global
health status represents a better QoL. A higher transformed score for Endocrine and GI
symptoms represents a higher level of symptomatology/problems
Baseline

Week 48

Week 96

LVA

QLQ-C30 Global health

status/QoL
LAN

70.2 (19.9) [n 70.9 (17.3) [n 66.4 (22.1) [n 64.5 (23.2) [n

= 98]
Placebo

= 71]

= 57]

= 98]

73.6 (19.6) [n 72.0 (14.9) [n 70.1 (22.2) [n 67.0 (22.4) [n

= 99]
= 59]
= 34]
= 102]

QLQ-GI.NET21 Endocrine
symptoms
LAN

10.9 (15.0) [n 11.0 (15.5) [n 11.1 (15.1) [n 11.7 (14.9) [n

= 98]
= 71]
= 56]
= 97]

Placebo

12.0 (16.9) [n 13.2 (18.0 [n 11.8 (11.3) [n 13.9 (19.0) [n

= 98]
= 48]
= 34]
= 102]

QLQ-GI.NET21
Gastrointestinal symptoms
LAN

17.1 (16.4) [n 19.9 (17.6) [n 15.3 (13.8) [n 18.2 (16.5) [n

= 98]
= 71]
= 56]
= 97]

Placebo

18.3 (18.0) [n 16.0 (14.3) [n 17.4 (17.3) [n 19.8 (18.5) [n

= 98]
= 58]
= 34]
= 102]

Disclosure
P. Ruszniewski: Ipsen: Consultant/advisory role; honoraria; research funding; partner is
Ipsen employee. Novartis: honoraria and research funding; M. Caplin: IPSEN: honoraria
for consultant/advisory role. NOVARTIS: Consulting fee, Advisory Committees or Review
Panels; LEXICON: Consulting fee, Advisory Committees or Review Panel; M. Pavel:
Ipsen: Consulting & Speaker role fee. Pfizer, Inc.: Consulting & Speaker role fee. Novartis
Pharmaceuticals: Consulting & Speaker role fee, research funding. Lexicon
Pharmaceuticals, Inc.: Consulting & Speaker role fee; J. Ćwikła: Ipsen:
Research Funding; A. Phan: Ipsen: Research Funding; M. Raderer: Speaker fee from:
Ipsen, Novartis Pharmaceuticals, Roche Pharmaceuticals, Pfizer, Inc., Bayer, Inc.,
Celgene; G. Cadiot: Ipsen: Consultant and Speaker fee. Novartis Pharmaceuticals:
Consultant and Speaker fee. Keocyt: Consultant and Speaker fee; G. Rindi: Ipsen:
Consultant and Speaker fee. Novartis Pharmaceuticals: Consultant and Speaker fee.
Pfizer, Inc.: Consultant and Speaker fee. Advanced Accelerator Applications: Consultant
fee; A. Langley: Ipsen: Consultant fee; J. Blumberg: Ipsen: employee; E. Gomez-Panzani:
Ipsen: employee. All other authors have declared no conflicts of interest.

Invited discussant abstracts 1134PD, 1135PD and 1136PD

K. Oberg (Uppsala, Sweden)

Questions to Discussant
K. Oberg

1137PD - Carcinoma of unknown primary: features and outcomes of patients

managed in a large UK centre
R. Lee (Manchester, United Kingdom)S. Baxter (Manchester, United Kingdom)
S. J. Ayers (Manchester, United Kingdom)C. L. Mitchell (Manchester, United Kingdom)
J. Hasan (Manchester, United Kingdom)
Aim
Carcinoma of unknown primary (CUP) is a metastatic epithelial or neuroendocrine

malignancy identified on final histology with no primary site detected despite investigations
and specialist review (National Institute of Clinical Excellence (NICE), UK). 3-5% of
malignancies are CUP with associated poor prognosis. In this retrospective case series
we reviewed the pathology and prognostic factors of patients (pts) with CUP and analysed
responses to chemotherapy (CT).
Methods
A retrospective review was performed on pts presenting between 2005 and 2011 with
confirmed CUP (as per NICE definition). Data from medical records, histological,
laboratory and radiological investigations were analysed. Univariate and multivariate
analysis was carried out to evaluate the effects of patient and disease characteristics
overall survival (OS).
Results
249 pts with suspected CUP were referred with 134 pts having histological confirmation.
Median age at diagnosis was 64.5 years (range 19 to 85 years); 54.5% male and 45.5%
female. Median OS for pts with confirmed CUP was 23.9 weeks (range 0.14-441 wks). On
univariate analysis overall predictors of decreased OS were raised lactate dehydrogenase
(P<0.001), performance status (PS) > = 2 (P<0.001), adenocarcinoma histology
(P<0.001), >1 organ affected (P < 0.001), presence of liver metastases (P = 0.002).
Predictors of better OS were squamous histology (P < 0.001), predominantly lymph node
involvement (P < 0.001), treatment with chemotherapy (P = 0.015) or surgery (P<0.001).
On multivariate analysis PS > = 2 (P < 0.001) was significant for decreased OS with a
trend for pts with adenocarcinoma (P = 0.07). Pts managed with surgery had superior
outcome compared to best supportive care (BSC) (median OS 68 vs 4 wks P<0.001);
chemotherapy (median OS 30 wks P < 0.001) or radiotherapy (median OS 18 wks) also
did significantly better. 60 pts received systemic chemotherapy with a variety of regimens.
Complete response was achieved in 4/60 pts, partial response in 9/60, stable disease in
13/60 and progressive disease in 18/60. 6 pts received second line treatment. Response
to chemotherapy significantly improved median OS. Multivariate analysis showed pts with
PS> = 2 (P < 0.001), >1 organ affected (P = 0.017) and liver metastases (P = 0.005) had
decreased OS. No significant difference in OS seen in pts receiving platinum or non
platinum chemotherapy.
Conclusions
CUP remains a difficult to treat entity and there are sub groups such as adenocarcinoma
and poor PS with very poor prognosis. It is important to have careful discussions with pts
regarding benefits of chemotherapy when their disease has adverse features.
Disclosure
All authors have declared no conflicts of interest.

1138PD - Activation status and prognostic significance of the Wnt/B Catenin and
Hedgehog/Smoothened signalling pathways in patients with cancer of unknown
primary (CUP): a translational research study of the Hellenic Cooperative Oncology
Group (HeCOG)
G. Pentheroudakis (Ioannina, Greece)G. Fotopoulos (Ioannina, Greece)A. Gousia (Athens, Greece)
M. Bobos (Athens, Greece)S. Chrysafi (Athens, Greece)G. Fountzilas (Thessaloniki, Greece)
N. Pavlidis (Ioannina, Greece)
Aim

The Wnt/b catenin and Hedgehog/Smoothened signalling pathways regulate cellular

proliferation, stemness, migratory and self-renewal potential, however their activation
status and prognostic utility have not been investigated in Cancer of Unknown Primary.
Methods
Tissue microarrays from 87 CUP patients were constructed and immunohistochemistry
(IHC) was succefully performed for Nuclear and cytoplasmic b-Catenin, nuclear TCF, LEF,
Gli1, cytoplasmic and nuclear Smoothened (SMO) in 56 cases.
Results
87 CUP patients harbouring CUP, mostly high-grade adenocarcinoma of visceral
(28,32.1%), serous peritoneal (22,25.2%) or neuroendocrine (18, 20.7%) subgroups were
retrospectively identified. Positive IHC expression (1% or more of staining cells) was seen
in 1/3-1/4 of cases for each marker. Positively correlated expression was found for nuclear
b-catenin with nuclear LEF, nuclear SMO. At a median follow-up of 85 months, only
nuclear SMO was prognostic for overall survival (OS, SMO+ cases median OS 19 vs 12
months, p = 0.01). When complex profiles of activated pathways were examined, IHC
activation of the Wnt pathway (positivity for any of the nuclear b-catenin and/or nuclear
TCF and/or nuclear LEF) was significantly associated with improved PFS, OS, the
significance mainly being driven by TCF and/or LEF nuclear expression (p = 0.04). In
multivariate analysis, IHC expression of nuclear TCF and/or LEF carried significantly
reduced risk of death (HR 0.15, p = 0.018).
Conclusions
Retrospective data suggest that activation of the Wnt pathway is associated with improved
outcome of CUP patients, with the nuclear expression of TCF or LEF being the most
reliable surrogate markers. In view of potential for therapeutic targeting, independent
validation in larger series is warranted.
Disclosure
All authors have declared no conflicts of interest.

1139PD - Clinical outcomes from the UK CUP-ONE Study: A multi-centre trial to

assess the efficacy of epirubicin, cisplatin and capecitabine (ECX) in carcinomas of
unknown primary (CUP) with prospective validation of molecular classifiers
H. Wasan (London, United Kingdom)J. Paul (Glasgow, United Kingdom)M. Nicolson (Aberdeen, United Kingdom)
T. Evans (Bearsden, Glasgow, United Kingdom)L. McMahon (Glasgow, United Kingdom)
A. Morris (Glasgow, United Kingdom)E. McCartney (Glasgow, United Kingdom)
C. Bridgewater (Sheffield, United Kingdom)D. Bowtell (Melbourne, Australia)
M. Erlander (San Diego, United States of America)K. Oien (Glasgow, Scotland, United Kingdom)
Aim
A multi-centre single-arm phase II trial of epirubicin, cisplatin and capecitabine (ECX) to
establish the efficacy of the ECX regimen, and an associated translational study
incorporating the prospective validation of molecular classifiers and exploratory
metabonomics.
Methods
CUP-ONE combines a multicentre phase II trial of epirubicin, cisplatin and capecitabine
(ECX) [Part 2] and a concurrent translational study [Part 1] incorporating blinded
prospective validation of 3 diagnostic molecular classifiers. 'Good' CUP subsets are

specifically excluded (i.e. mid-line tumours, germ-cell origin, isolated axillary or neck
lymphodenopathy and neuroendocrine). Part 2 assessed treatment outcomes to evaluate,
after exclusion of the 'best' CUP subsets, ECX was a valuable treatment. This was
formally assessed by overall RECIST response rate (ORR) using a Simon's two-stage
minimax design to test the null hypothesis that the true ORR is <20% versus the
alternative that it is >= 40% (95% power, 5% 1-sided). This required 57 patients.
Secondary endpoints were progression- free survival (PFS), overall survival (OS) and
quality of life (QoL).
Results
Since February 2010, CUP-ONE has recruited 531 patients to Part 1 (still open) and 59 to
Part 2 (54 in both). Part 2 closed to recruitment in February 2013. Results are presented
for 58 eligible patients. Demographics: Male 47%, female 53%. ECOG PS 0: 38%, 1:
62%. Median age: 63 (range 29- 78). 91% Stage IV, 5% Stage III. 81% adenocarcinoma,
5% squamous carcinoma, 50% poorly or undifferentiated pathology. Study therapy: 30%
completed 8 cycles of ECX (median 5 cycles). Efficacy: The null hypothesis was rejected
with an estimated ORR of 35% (90% CI 25%- 47%; CR 7%; PR 28%; SD 26%, PD 30%).
Median PFS 6.9 months (80% CI 4.8, 7.8), median OS 10.2 months (80% CI 8.3, 11.1).
Treatment toxicities were acceptable with 54% recording worst AE grade <3.
Conclusions
CUP-ONE is the largest prospective CUP trial incorporating detailed diagnostic
biomarkers including gene expression profiling. After excluding 'best' prognosis CUP
patients, ECX proved an active and well- tolerated regimen. Correlation with translational
outputs and QoL analysis is ongoing.
Disclosure
All authors have declared no conflicts of interest.

Invited discussant abstracts 1137PD, 1138PD and 1139PD

B. Skogseid

Questions to Discussant
1140PD - Finding molecular subgroups of worse prognosis studying the
microenvironment of gastro-entero-pancreatic neuroendocrine tumours (GEP-NET).
J. Barriuso (Madrid, Spain)E. Bernal (Madrid, Spain)L. G. Pastrian (Madrid, Spain)J. Martinez (Madrid, Spain)
E. Diaz (Madrid, Spain)V. Heredia (Madrid, Spain)M. Miguel (Madrid, Spain)C. Alvarez-Escola (Madrid, Spain)
J. Castell (Madrid, Spain)J. Feliu (Madrid, Spain)E. Burgos (Madrid, Spain)M. Mendiola (Madrid, Spain)
Aim
Tumour suppressor genes, CDKN1B and PTEN, are commonly altered in GEP-NET.
However, their role is not completely understood yet. The aim of this study was to link the
expression of their products (p27 and PTEN) with proteins of the GEP-NET
microenvironment.
Methods
Formalin-fixed and paraffin-embedded samples (FFPEs) of patients (pts) who underwent
surgery for GEP-NET and their clinical data were collected consecutively from 1980 to
2012. The study was approved by the local Ethics Committee. Tissue microarrays were
constructed from non-necrotic areas of tumour foci. We performed a stratified analysis of

proteins related to the extracellular matrix and the epithelial to mesenchymal transition
process by inmunohistochemistry-measured PTEN and P27. Kaplan-Meier method and
log rank test was used for the univariate survival analysis and Cox regression was used
for the multivariate analysis (MSA).
Results
A total of 115 FFPEs were analysed. Median follow up was 12 years. Median age was 46
years; 49.6% female; 67.8% intestinal. PTEN was evaluated as presence vs absence and
P27 as strong nuclear staining vs weak or absence. P27 and PTEN were independent
prognostic factors for disease free survival (DFS) when adjusted by grade and stage, p =
0.028 and p = 0.023 respectively. Within the PTEN negative subgroup, LOXL2 + conferred
protection for relapse, p < 0.001 and remained significant in the MSA, HR: 0.06 95%CI:
0.01-0.63; B-catenin nuclear expression (BCATn) was a marker of bad prognosis, p =
0.043. Within P27- cases, LOXL2 + had longer DFS (p = 0.01) and a HR: 0.25 95%CI:
0.08-0.83 in the MSA; CXCR4 + and BCATn had shorter DFS (p = 0.035 and p = 0.005)
but were not significant in the MSA.
CXCR4 +
P27-

CXCR4- LOXL2 + LOXL2-

55.9 (0.1-132.8) NR

PTEN- NC

NC

BCATm BCATn

NR

7.2 (4.6-7.8) NR

124.1 (16.7-231.5)

NR

0.4 (0.1-2.2) NR

124.1 (35.3-212.9)

DFS medians calculated in months by Kaplan Meier method. BCATm: -catenin

membranous staining. NR: not reached. NC: not calculated.
Conclusions
Patients with P27 LOXL2 or PTEN LOXL2 had the worst prognosis. These findings
warrant further in vitro mechanistically experiments and prospective clinical analysis.
Disclosure
All authors have declared no conflicts of interest.

1141PD - Gastroenteropancreatic Neuroendocrine Tumors (GEPNET) Registry:

Update from an International Collaboration
S. Yalcin (Ankara, Turkey)S. Glasberg (Jerusalem, Israel)H. Abali (Adana, Turkey)F. Aykan (Istanbul, Turkey)
L. Bai (Taichung, Taiwan)J. Kattan (Beirut, Lebanon)H. Lim (Singapore, Singapore)Y. Park (Seoul, Korea, Republic of)
H. Raef (Riyadh, Saudi Arabia)J. Ramos (Johannesburg, South Africa)K. Rau (Kaohsiung, Taiwan)
S. Saglam (Istanbul, Turkey)S. Serdengecti (Istanbul, Turkey)A. Sevinc (Gaziantep, Turkey)
Y. Shan (Tainan, Taiwan)Y. Shyr (Taipei, Taiwan)V. Sriuranpong (Bangkok, Thailand)S. N. Turhal (Istanbul, Turkey)
K. Yeh (Taipei, Taiwan)T. Hwang (Taoyuan, Taiwan)
Aim
Epidemiologic data for GEPNET is lacking in many geographic areas. The aim of the
GEPNET Registry is to study the prevalence, incidence, regional trends in diagnosis, and
clinical management of GEPNET in the Asia-Pacific, Middle East, Turkey and South
Africa.
Methods
Patients (pts) with histopathological diagnosis of GEPNET within 5 years (yrs) of registry
entry were included. Pro- and retrospective data were collected at 82 sites. Enrollment in
the registry was from July 2009 to December 2012. Follow-up will be for 5 yrs.
Results
As of December 1, 2013 (cut-off for this interim analysis), 1005 pts were enrolled, 933

were evaluable. At diagnosis, median age was 54 yrs [range: 12-87], gender ratio was
balanced (49% male). The majority of pts (740/933, 77%) had symptoms at the time of
diagnosis. Abdominal pain and weight loss were the most commonly reported symptoms.
The most frequently reported primary site was the pancreas (42%) followed by the
stomach (17%). The majority of pts had well-differentiated tumors (70%). Immunostaining
results for Synaptophysin and Chromogranin A were reported for the majority of patients
(77% and 82% respectively). Proliferative indices were less frequently reported; mitotic
index: 17% and Ki-67: 50% pts. Use of computed tomography scanning was the main
modality of disease evaluation (44% pts). Other imaging modalities including functional
PET and octreotide scintigraphy were used in <10% pts at diagnosis. The use of serum
CgA testing at diagnosis and 24 h urine 5HIAA tests were rarely used (11% and 7% pts),
although there was substantial variation by geographic region. The most common initial
therapy was surgery (60%) followed by somatostatin analogues (17%) and chemotherapy
(16%). Median progression free survival was 57.3 months (95%CI: 52.2- 64.4), and varied
by primary tumor site as well as WHO (2004) classification at diagnosis.
Conclusions
The GEPNET Registry continues to provide important information as it relates to the
diagnosis and treatment of patients in the participating countries. This analysis has
highlighted the need for clinical practice improvement to ensure better evaluation of
patients.
Disclosure
S. Yalcin: Member of Novartis Advisory Board; Institution participates in
Novartis-sponsored clinical trials. S. Glasberg: Member of Novartis Advisory Board;
Institution participates in Novartis-sponsored clinical trials; H. Abali: Member of Novartis
Advisory Board; Institution participates in Novartis-sponsored clinical trials; F. Aykan:
Member of Novartis Advisory Board; Institution participates in Novartis-sponsored clinical
trials; L. Bai: Member of Novartis Advisory Board; Institution participates in
Novartis-sponsored clinical trials; J. Kattan: Member of Novartis Advisory Board;
Institution participates in Novartis-sponsored clinical trials; H.Y. Lim: Member of Novartis
Advisory Board; Institution participates in Novartis-sponsored clinical trials; Y.S. Park:
Member of Novartis Advisory Board; Institution participates in Novartis-sponsored clinical
trials; H. Raef: Member of Novartis Advisory Board; Institution participates in
Novartis-sponsored clinical trials; J. Ramos: Member of Novartis Advisory Board;
Institution participates in Novartis-sponsored clinical trials; K. Rau: Member of Novartis
Advisory Board; Institution participates in Novartis-sponsored clinical trials; S. Saglam:
Member of Novartis Advisory Board; Institution participates in Novartis-sponsored clinical
trials; S. Serdengecti: Member of Novartis Advisory Board; Institution participates in
Novartis-sponsored clinical trials; A. Sevinc: Member of Novartis Advisory Board;
Institution participates in Novartis-sponsored clinical trials; Y. Shan: Member of Novartis
Advisory Board; Institution participates in Novartis-sponsored clinical trials; Y. Shyr:
Member of Novartis Advisory Board; Institution participates in Novartis-sponsored clinical
trials.; V. Sriuranpong: Member of Novartis Advisory Board; Institution participates in
Novartis-sponsored clinical trials; S.N. Turhal: Member of Novartis Advisory Board;
Institution participates in Novartis-sponsored clinical trials; K. Yeh: Member of Novartis
Advisory Board; Institution participates in Novartis-sponsored clinical trials; T. Hwang:
Member of Novartis Advisory Board; Institution participates in Novartis-sponsored clinical
trials.

1142PD - Large Cell Neuroendocrine Carcinomas (LCNEC) of the lung: Pathologic

features, treatment and outcomes
J. Naidoo (New York, United States of America)M. L. Santos-Zabala (New York, United States of America)
T. Iyriboz (New York, United States of America)K. Woo (New York, United States of America)
C. S. Sima (New York, United States of America)J. J. Fiore (New York, United States of America)
M. Kris (New York, United States of America)S. R. Veach (New York, United States of America)
G. J. Riely (New York, United States of America)A. Iqbal (New York, United States of America)
S. Smith-Marrone (New York, United States of America)I. S. Sarkaria (New York, United States of America)
L. M. Krug (New York, United States of America)C. M. Rudin (New York, United States of America)
N. Rekhtman (New York, United States of America)M. Pietanza (New York, United States of America)
Aim
LCNEC is a rare thoracic malignancy, for which pathologic classification and optimal
therapies are debated. We report the largest series of stage IV LCNECs, evaluating
clinicopathologic features, treatment and survival.
Methods
Pts with stage IV LCNEC evaluated at MSKCC from 2006-2013 were identified.
Clinicopathologic and treatment data were collected. Radiologic RECIST evaluation was
performed for pts with existing diagnostic imaging. Pts with available tissue underwent
pathology re-review to confirm diagnosis, and potentially identify features that could
impact outcomes.
Results
50 pts were identified (median age: 66 years; 62% male; 88% former/current smokers).
Common sites of metastasis: lymph nodes (n = 29); brain (n = 22); liver (n = 13). 34% of
pts had diagnostic molecular testing with PCR-based fragment length analysis, mass
spectrometry based assay for point mutation genotyping, and ALK FISH testing: 24% had
KRAS mutations (mtns) (n = 4/17; G12D, n = 2; G12C, n = 1; Q61H, n = 1). No EGFR
mtns or ALK rearrangements were noted. 33 pts had archived tumor at MSKCC for central
pathology re-review. The diagnosis of LCNEC was confirmed in all but 2 cases, which
were reclassified as SCLC and combined SCLC/LCNEC (both brain metastases),
respectively. Treatment data was available on 39 pts: 77% (n = 30) received first-line
platinum(plt)/etoposide. 23% (n = 9) received other regimens: plt/taxane (n = 4),
plt/pemetrexed (n = 1), plt/pemetrexed/bevacizumab(bev) (n = 1), temozolomide (n =
1)/bev (n = 1), clinical trial (n = 1). Objective response rate was 32% with plt/etoposide by
RECIST (95% CI: 16-52%). Median OS was 12.2mos (range: 9-19.3mos) for all pts.
Karnofsky performance status <80 and LDH >250 were poor prognostic factors for OS on
multivariate analysis (p < 0.05).
Conclusions
Pts with stage IV LCNEC have low response to plt/etoposide treatment and poor OS.
KRAS mutations are commonly observed. Prospective studies are needed to investigate
optimum therapeutic strategies.
Disclosure
All authors have declared no conflicts of interest.

Invited discussant abstracts 1140PD, 1141PD and 1142PD

P. Ruszniewski (Clichy, France)

Questions to Discussant