Update on neuroendocrine tumors - OncologyPRO

GASTROENTEROPANCREATIC NEUROENDOCRINE

TUMORS

Update on neuroendocrine tumors

Nicola Fazio, M.D., Ph. D.

Division of Gastrointestinal Medical Oncology

and Neuroendocrine Tumors

European Institute of Oncology

Milan, Italy

3rd ESO-ESMO-RCE Preceptorships & Clinical Update on Rare Adult SolidCancers

01.12.2018 - 03.12.2018

Milan, Italy

ADVANCED COURSES & SEMINARS

Rare genito-urinary cancers, Rare gynaecological cancers, Rare head and neck cancers, Rare

tumors, Sarcoma

* Third party registration should be used if you are requesting an individual registration for

someone who is not you.

Please note that website registration under your name will be needed before registering

someone else to this event.

Programme

PRECEPTORSHIPS ON RARE ADULT SOLID CANCERS

1 December8:30 Registration and coffee entry

8:50 Welcome

P.G. Casali, IT

INTRODUCTION (plenary)

9:00 Epidemiology and rare cancer networking

A. Trama, IT

9:30 The pathologic diagnosis

A.P. Dei Tos, IT

10:00 Clinical decision making in RC

3rd ESO-ESMO-RCE Preceptorships & Clinical Update on Rare Adult SolidCancers

01.12.2018 - 03.12.2018

Milan, Italy

ADVANCED COURSES & SEMINARS

Rare genito-urinary cancers, Rare gynaecological cancers, Rare head and neck cancers, Rare

tumors, Sarcoma

* Third party registration should be used if you are requesting an individual registration for

someone who is not you.

Please note that website registration under your name will be needed before registering

someone else to this event.

Programme

PRECEPTORSHIPS ON RARE ADULT SOLID CANCERS

1 December8:30 Registration and coffee entry

8:50 Welcome

P.G. Casali, IT

INTRODUCTION (plenary)

9:00 Epidemiology and rare cancer networking

A. Trama, IT

9:30 The pathologic diagnosis

A.P. Dei Tos, IT

10:00 Clinical decision making in RC

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DISCLOSURE

◆ Personal financial interests:

Novartis, Ipsen, Pfizer, Merck Serono, Advanced Accelerator Applications, MSD

◆ Institutional financial interests:

Novartis, Ipsen, Merck Serono, MSD, Pharmacyclics, Incyte, Halozyme, Roche,

Astellas, Pfizer

◆ Non-financial interests:

• ESMO Coordinator of the Neuroendocrine, Endocrine neoplasms and CUP Faculty

• ENETS (European Society of Neuroendocrine Tumors) advisory board member

• AIOM coordinator for neuroendocrine neoplasms guidelines

• ITANET Scientific committee member, Member of the task force for interaction with

patients associationsDo not duplica

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OBJECTIVES

❖ To describe epidemiology and clinical

characteristics of GEP NEN

❖ To review the management of patients with

advanced disease

❖ To summarize the main recent new insights


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Nicola Fazio, M.D., Ph.D. IEO, European Institute of Oncology, IRCCS, Milan

GEP NENs: European epidemiological data


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G1

(Ki-67 < 2% and/or MI < 2)

G2

(Ki-67 3-20% and/or MI 2-20)

G3

(Ki-67 > 20% and/or MI > 20)

WHO 2010 GI NEN classification

NET

(Tumours)

NEC

(Carcinomas)


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G1

(Ki-67 < 2% and/or MI < 2)

G2

(Ki-67 3-20% and/or MI 2-20)

G3

(Ki-67 > 20% and/or MI > 20)

WHO 2017 Pancreatic NEN classification

G3

(Ki-67 > 20% and/or MI > 20)

NET

(Tumours)

NEC

(Carcinomas)Do not duplica

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Survival is related to the

stage, grade and primary site.

Dasari, JAMA Oncol 2017


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Midgut

GI extra-midgut

Pancreas

GEP NENs


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http://www.google.it/url?sa=i&rct=j&q=&esrc=s&frm=1&source=images&cd=&cad=rja&docid=dFOf4EbLdIfY_M&tbnid=fltyE1WlVzYP2M:&ved=0CAUQjRw&url=http://www.andreamilitello.it/ecografia/malattie_del_pancreas.html&ei=huJhUfLiKIfBPIrLgbgC&bvm=bv.44770516,d.bGE&psig=AFQjCNHDm4RVg-AsZgMAS_R3vbSXR28dwA&ust=1365455875542992

GEP NET: clinical presentation

At diagnosis mainly:

✓ Advanced (mostly liver)

✓ Non functioning (no clinical syndrome)

✓ Sporadic

✓ SSTR-2 positive (at 68Ga-DOTA-peptide-PET/CT)

Cives et al., CA Cancer J Clin 2018


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GEP NETs: clinical syndromes

Dimitriadis et al., End Rel Cancer 2016


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OBJECTIVES




advanced disease



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Phase III trials with Octreotide and Lanreotide

as antiproliferative therapy in GEP NET patients

Rinke et al., JCO 2008

Caplin et al., NEJM 2013Do not duplicate or d

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Everolimus Investigation in GEP NETs

RADIANT (RAD001 in Advanced Neuroendocrine Tumors)

2005 2006 2007 2008 2009 2010 2011 2012 2013 2014

RADIANT-3

RADIANT-2

RADIANT-1

RADIANT-4

Phase III

Phase II

Yao et al., JCO 2008

Yao et al., NEJM 2011

Pavel et al., Lancet 2012

Yao et al., Lancet 2016Do not duplicate or d

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Phase III Phase IV

Sunitinib in advanced PanNET patients

Phase II

2003 2005 2007 2009 2012 2015

Kulke et al., JCO 2008

Raymond et al., NEJM 2011

Raymond et al., Neuroendocrinology 2018


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NETTER-1

Phase III trial of PRRT in midgut NET patients

2012 2013 2014 2015 2016

Strosberg et al., NEJM 2017Do not duplicate or d

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‘70 ’80 ’90 2011

STZ in

panNET

Octreotide

IFN in carcinoid

syndrome

Lanreotide

in carcinoid

syndrome

Sunitinib

Everolimus

in panNET

PRRT in

GEP NET

FDA/EMA approved therapies for patients with advanced GEP NETs

2015

Lanreotide in

GEP

Octreotide in

midgut

2016

Everolimus in

non functioning

Lung and GI

Telotristatin refractory

carcinoid syndrome

diarrhea

2017


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No validated predictive biomarker for sunitinib and everolimus

Martins et al., Targeted Oncol 2017

REVIEW ARTICLE

Predictive Markers of Response to Everolimus and Sunitinibin Neuroendocrine Tumors

Diana Martins1&Francesca Spada1

&Ioana Lambrescu1&Manila Rubino1

&

Chiara Cella1&Bianca Gibelli 2 &Chiara Grana3

&Dario Ribero4&Emilio Bertani 4 &

DavideRavizza5&Guido Bonomo6

&Luigi Funicelli 7&Eleonora Pisa8

&Dario Zerini 9 &

Nicola Fazio1&IEO ENETS Center of Excellence for GEP NETs

# Springer International Publishing Switzerland 2017

Abstract Neuroendocrine tumors (NETs) represent a large

and heterogeneous group of malignancies with various bio-

logical and clinical characteristics, depending on the site of

origin and the grade of tumor proliferation. In NETs, as in

other cancer types, molecularly targeted therapies have radi-

cally changed the therapeutic landscape. Recently two

targeted agents, the mammalian target of rapamycin inhibitor

everolimus and the tyrosine kinase inhibitor sunitinib, have

both demonstrated significantly prolonged progression free

survival in patients with advanced pancreatic NETs. Despite

these important therapeutic developments, there are still sig-

nificant limitationsto theuseof theseagentsdueto thelack of

accuratebiomarkers for predicting tumor responseand effica-

cy of therapy. In this review, we provide an overview of the

current clinical data for theevaluation of predictive factorsof

response to/efficacy of everolimus and sunitinib in advanced

pancreatic NETs. Surrogate indicators discussed include cir-

culating and tissue markers, as well as non-invasive imaging

techniques.

Key Points

Everolimus and sunitinib are widely investigated

targeted cancer therapies, and they are both globally

approved by regulatory authorities for the treatment of

pancreatic NETs.

The establishment of predictive markers of response to

everolimus and sunitinib in NETs is of extreme importance

for their efficient use.

Most efforts to define predictive biomarkers have failed,

with the exception of chromogranin-A and neuron-specific

enolase for advanced pancreatic NETs treated with

everolimus.

1 Introduction

Neuroendocrine tumors (NETs) comprise a heterogeneous

group of malignanciesoriginating from the diffuseendocrine

system. Even though NETsareconsidered a raremalignancy,

representing about two new cases per 100.000 persons per

year, their incidenceand prevalenceseem to berising steadily

[1]. Someof thepossible reasons for the increasing incidence

* Nicola Fazio

[email protected]

1 Unit of Gastrointestinal Medical Oncology and Neuroendocrine

Tumors, European Instituteof Oncology, IEO, 20141 viaRipamonti,

435 Milan, Italy

2 Division of Otolaryngology-Head and Neck Surgery, European

Instituteof Oncology, IEO, Milan, Italy

3 Division of Nuclear Medicine, European Instituteof Oncology, IEO,

Milan, Italy

4 Division of Hepatobiliopancreatic Surgery, European Instituteof

Oncology, IEO, Milan, Italy

5 Division of Endoscopy, European Instituteof Oncology, IEO,

Milan, Italy

6 Division of Interventional Radiology, European Instituteof

Oncology, IEO, Milan, Italy

7 Division of Radiology, European Instituteof Oncology, IEO,

Milan, Italy

8 Division of Pathology, European Institute of Oncology, IEO,

Milan, Italy

9 Division of Radiotherapy, European Instituteof Oncology, IEO,

Milan, Italy

Targ Oncol

DOI 10.1007/s11523-017-0506-5


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In patients with advanced GEP NET

there is no absolute evidence about

a specific sequence or integration of

therapies


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Oncological scientific societes NEN scientific societes

Italian NEN guidelines

NET guidelinesfrom several different scientific societes


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SSA

1 2 4 53

Clinical trials

Liver-directed

treatments

Primary tumor

removal

Metastatic NF G2 SSTR-2 + small bowel NET

Everolimus

PRRT


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PRRT

Chemotherapy

Everolimus

Sunitinib

SSA

1 2 4 53

Clinical trials

Liver-directed

treatments

Primary tumor

removal

Metastatic NF G2 SSTR-2 + panNET


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GETNE-1206 (SEQTOR): Phase III Study in Patients With

Advanced pNET

Unpublished data. Clinicaltrials.gov ID, NCT02246127.

Primary end point: rate of second PFS at 84 weeks of treatment

Progression

Everolimus

STZ +

5-FU

Everolimus

STZ +

5-FU

Arm A:

Arm B:

Compare efficacy and safety of everolimus followed by chemotherapy with

STZ + 5-FU upon progression, or the reverse sequence (chemotherapy with

STZ + 5-FU followed by everolimus upon progression)

26

GETNE 1206 (SEQTOR) phase III trial

in patients with advanced panNETs

enrolling


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177Lu-edotreotide

Everolimus

Rand. 2:1

Phase III

G1-G2 SSTR-2 +++, advanced progressive GEP NET

COMPETE trial


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TEM alone or CAP-TEM in PanNET?

Kunz, ASCO 2018 oral presentationDo not duplicate or d

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Original Paper

Neuroendocrinology

Efficacy and Safety of Sunitinib in Patients with Well-Differentiated Pancreatic Neuroendocrine Tumours

Eric Raymond

a Matthew H. Kulke

b Shukui Qin

c Xianjun Yu

d Michael Schenker

e

Antonio Cubillo

f Wenhui Lou

g Jiri Tomasek

h Espen Thiis-Evensen

i Jian-Ming Xu

j

Adina E. Croitoru

k Mustafa Khasraw

l Eva Sedlackova

m Ivan Borbath

n Paul Ruff

o

Paul E. Oberstein

p Tetsuhide Ito

q Liqun Jia

r Pascal Hammel

s Lin Shen

t

Shailesh V. Shrikhande

u Yali Shen

v Jozef Sufliarsky

w Gazala N. Khan

x Chigusa Morizane

y

Salvatore Galdy

z Reza Khosravan

A Kathrine C. Fernandez

B Brad Rosbrook

A Nicola Fazio

z

a Department of Medical Oncology, Paris Saint-Joseph Hospital Group, Paris, France; b

Program in Neuroendocrine

and Carcinoid Tumors, Dana-Farber Cancer Institute, Boston, MA, USA; c PLA Cancer Center, Nanjing Bayi Hospital,

Nanjing, China; d Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center, Shanghai,

China; e Centrul de Oncologie Sf. Nectarie, Oncologie Medicala, Craiova, Romania; f Hospital Universitario Madrid

Sanchinarro, Centro Integral Oncológico Clara Campal, Madrid, Spain; g Zhongshan Hospital, Fudan University,

Shanghai, China; h Faculty of Medicine, Masaryk Memorial Cancer Institute, Masaryk University, Brno, Czech

Republic; i Department of Gastroenterology, Oslo University Hospital, Rikshospitalet, Oslo, Norway; j No. 307

Hospital, Academy of Military Medical Sciences, Beijing, China; k Department of Medical Oncology, Fundeni Clinical

Institute, Bucharest, Romania; l Andrew Love Cancer Center, Geelong Hospital, Victoria, VIC, Australia; m

Všeobecné

Fakultní Nemocnice v Praze Onkologická Klinika, Prague, Czech Republic; n Hepato-Gastroenterology Department,

Cliniques Universitaires Saint-Luc, Brussels, Belgium; o Faculty of Health Sciences, University of the Witwatersrand,

Johannesburg, South Africa; p Division of Hematology/Oncology, Columbia University Medical Center, New York,

NY, USA; q Department of Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu

University, Fukuoka, Japan; r China-Japan Friendship Hospital, Beijing, China; s

Service d’Oncologie Digestive, Hôpital

Beaujon, Clichy, France; t Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education),

Department of GI Oncology, Peking University Cancer Hospital and Institute, Beijing, China; u GI and HPB Surgical

Oncology, Tata Memorial Hospital, Mumbai, India; v West China Hospital of Sichuan University, Chengdu, China;

w 2nd Department of Oncology, Faculty of Medicine, Comenius University, Bratislava, Slovakia; x

Henry Ford Health

System, Detroit, MI, USA; y National Cancer Center, Tokyo, Japan; z

Division of Gastrointestinal Medical Oncology and

Neuroendocrine Tumors, European Institute of Oncology, IEO, Milan, Italy; A Pfizer Oncology, Pfizer Inc., San Diego,

CA, USA; B Pfizer Oncology, Pfizer Inc., Cambridge, MA, USA

Received: March 11, 2018

Accepted after revision: July 5, 2018

Published online: July 10, 2018

Nicola FazioDivision of Gastrointestinal Medical Oncology and Neuroendocrine TumorsEuropean Institute of Oncology, IEOVia Ripamonti 435, IT–20143 Milan (Italy)E-Mail nicola.fazio @ ieo.it

© 2018 S. Karger AG, Basel

E-Mail [email protected]

www.karger.com/nen

DOI: 10.1159/000491999

Keywords

Pancreatic neuroendocrine tumour · Progression-free

survival · Overall survival · Safety · Sunitinib

Abstract

Background: In a phase III study, sunitinib led to a significant

increase in progression-free survival (PFS) versus placebo

in patients with pancreatic neuroendocrine tumours (pan-

NETs). This study was a post-marketing commitment to sup-

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193.

204.

98.2

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10/

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7:45

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PM

Raymond et al.Neuroendocrinology4DOI: 10.1159/000491999

PFS d

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1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

0 10 15 20 25

Time, months

6145

4129

3220

1410

88

64

04

02

01

00

30 35 40 45

Number at risk:Treatment-naive

Previously treated

a

n Events mPFS (95% CI), monthsTreatment-naive 61 37 13.2 (7.4–16.8)Previously treated 45 28 13.0 (9.2–20.4)

5

PFS d

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1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

0.2

0.1

0

0 10 15 20 25

Time, months

6145

2925

2217

1111

68

45

14

02

00

00

30 35 40 45


Previously treated

c

n Events mPFS (95% CI), monthsTreatment-naive 61 25 18.7 (5.6–NE)Previously treated 45 24 16.5 (7.4–22.9)

5

PFS d

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1.0

0.9

0.8

0.7

0.6

0.5

0.4

0.3

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0 10 15 20 25

Time, months

6145

3026

2215

99

37

15

04

02

00

––

30 35 40 45


Previously treated

b

n Events mPFS (95% CI), monthsTreatment-naive 61 31 11.1 (5.5–16.7)Previously treated 45 26 9.5 (7.4–18.4)

5

Fig. 1. Kaplan-Meier estimates of progres-sion-free survival in treatment-naive and previously treated patients with panNETs (full analysis set). a Assessed by investiga-tors. b Assessed by independent third-par-ty radiology according to RECIST v1.0. c Assessed by independent third-party radi-ology according to Choi criteria. CI, confi-dence interval; mPFS, median progression-free survival; NE, not estimable; panNET, pancreatic neuroendocrine tumour; RE-CIST, Response Evaluation Criteria in Sol-id Tumours.

Do

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19

3.2

04

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.21

0 -

10

/10

/20

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7:4

5:1

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ORR in PanNET phase IV sunitinib trial: RECIST vs. ChoiSupplementary Table S2. Summary of efficacy measures according to independent

radiologic review (full analysis set)

Treatment-naive

cohort

(n = 61)

Previously treated

cohort

(n = 45)

Total

population

(N = 106)

Objective tumour response per RECIST v1.0 criteria

Best overall response, n (%)

Complete response 0 1 (2.2) 1 (<1.0)

Partial response 14 (23.0) 8 (17.8) 22 (20.8)

Stable disease 34 (55.7) 34 (75.6) 68 (64.2)

Progressive disease 10 (16.4) 2 (4.4) 12 (11.3)

Missing 3 (4.9) 0 3 ( 2.8)

Objective response rate 14 (23.0) 9 (20.0) 23 (21.7)

95% exact CIa 13.2–35.5 9.6–34.6 14.3–30.8

Objective tumour response per Choi criteria


Complete response 0 1 (2.2) NR

Partial response 32 (52.5) 24 (53.3) NR

Stable disease 12 (19.7) 17 (37.8) NR

Progressive disease 9 (14.8) 2 (4.4) NR

Missing 8 (13.1) 1 (2.2) NR

Objective response rate 32 (52.5) 25 (55.6) NR

95% exact CIa 39.3–65.4 40.0–70.4 NR

Time to tumour progression per Choi criteria

Median (95% CI)b time to progression, 18.7 (5.6–NE) 16.7 (7.4–30.9) NR

Supplementary Table S2. Summary of efficacy measures according to independent


Treatment-naive

cohort

(n = 61)

Previously treated

cohort

(n = 45)

Total

population

(N = 106)





Stable disease 34 (55.7) 34 (75.6) 68 (64.2)


Missing 3 (4.9) 0 3 ( 2.8)


95% exact CIa 13.2–35.5 9.6–34.6 14.3–30.8







Missing 8 (13.1) 1 (2.2) NR


95% exact CIa 39.3–65.4 40.0–70.4 NR





Treatment-naive

cohort

(n = 61)

Previously treated

cohort

(n = 45)

Total

population

(N = 106)





Stable disease 34 (55.7) 34 (75.6) 68 (64.2)


Missing 3 (4.9) 0 3 ( 2.8)


95% exact CIa 13.2–35.5 9.6–34.6 14.3–30.8







Missing 8 (13.1) 1 (2.2) NR


95% exact CIa 39.3–65.4 40.0–70.4 NR





Treatment-naive

cohort

(n = 61)

Previously treated

cohort

(n = 45)

Total

population

(N = 106)





Stable disease 34 (55.7) 34 (75.6) 68 (64.2)


Missing 3 (4.9) 0 3 ( 2.8)


95% exact CIa 13.2–35.5 9.6–34.6 14.3–30.8







Missing 8 (13.1) 1 (2.2) NR


95% exact CIa 39.3–65.4 40.0–70.4 NR



Raymond et al., Neuroendocrinology 2018Do not duplica

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Advanced 2016 ENETs guidelines

“Patients with 5–20% Ki-67 pNET can be treated

with chemotherapy”

“Factors that favour chemotherapy compared with targeted therapies:

✓ Bulky disease;

✓ Symptomatic patient;

✓ Rapid tumour progression in ≤ 6–12 months;

✓ Patients with a possible chance of achieving a response to

allow for surgery (neoadjuvant option)”

Pavel M, et al. Neuroendocrinology 2016


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G3 GEP NENs


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In NET G3 biological therapies,

PRRT and liver-directed

treatments should be considered


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OBJECTIVES




advanced disease



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New TKIs


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Novel TKIs in GEP NETs

Phase III

Phase III

Phase III


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Capdevila, NET proferred paper session, ESMO 2018Do not duplicate or d

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Immune checkpoint inhibitors


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PDR001 in GEP and Lung NET/NEC

Phase II multi-cohort international study

PDR001 binds to PD-1 so blocking

both PD-L1 and PD-L2▪ Well differentiated:

▪ GI cohort (n=30)

▪ Pancreatic cohort (n=30)

▪ Thoracic cohort (n=30)

▪ Poorly differentiated:

▪ GEP cohort (n=20)


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Statistical assumption: at least 10% PR

Yao, ESMO 2018 NET Proferred Paper SessionDo not duplica

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Yao, NET proferred paper session, ESMO 2018Do not duplicate or d

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Pentheroudakis, ESMO 2018 NET Highlights


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1

Pembrolizumab for Patients With PD-L1–Positive Advanced Carcinoid or Pancreatic Neuroendocrine Tumors: Results From the KEYNOTE-028 StudyJanice M. Mehnert,1 Emily Bergsland,2 Bert H. O’Neil,3 Armando Santoro,4 Jan H. M. Schellens,5 Roger B. Cohen,6

Toshihiko Doi,7 Patrick A. Ott,8 Michael J. Pishvaian,9 Igor Puzanov,10 Kyaw L. Aung,11 Chiun Hsu,12

Christophe Le Tourneau,13 Jean-Charles Soria,14 Elena Élez,15 Kenji Tamura,16 Marlena Gould,17 Guoqing Zhao,17

Karen Stein,17 Sarina A. Piha-Paul18

1Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA; 2University of California San Francisco, San Francisco, CA, USA; 3Indiana University,

Simon Cancer Center, Indianapolis, IN, USA; 4Humanitas Research Hospital-Humanitas Cancer Center, Rozzano-Milano, Italy; 5Netherlands Cancer

Institute, Amsterdam, Netherlands; 6University of Pennsylvania, Philadelphia, PA, USA; 7National Cancer Center Hospital East, Chiba, Japan; 8Dana-

Farber Cancer Institute, Boston, MA, USA; 9Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USA; 10Roswell Park

Cancer Institute, Buffalo, NY, USA; 11Princess Margaret Cancer Centre, Toronto, ON, Canada; 12National Taiwan University Hospital, Taipei, Taiwan; 13Institut Curie, Paris, France; 14Institut Gustave Roussy Cancer Center, Villejuif, France; 15Vall d'Hebron University Hospital and Vall d'Hebron Institute of

Oncology (VHIO), Barcelona, Spain; 16National Cancer Center Hospital, Tokyo, Japan; 17Merck and Co., Inc., Kenilworth, NJ, USA; 18The University of

Texas MD Anderson Cancer Center, Houston, TX, USA

*Response assessment: Every 8 weeks for first 6 months; every 12 weeks thereafter

Primary endpoints: ORR per RECIST v1.1 (investigator review)

Secondary endpoints: PFS, OS, duration of response, and safety

KEYNOTE-028 (NCT02054806): Phase 1b Multicohort Study of Pembrolizumab for PD-L1+ Advanced Solid Tumors

Response

Assessment*

Pembrolizumab

10 mg/kg IV

Q2W

CR, PR, or SD

Treat for 24 months

or until

progressionb or

intolerable toxicity

Confirmed PDb or

unacceptable

toxicity

Discontinue

pembrolizumab

Patients

• Carcinoid tumors or

well or moderately

differentiated pNETs

• Failure of or inability to

receive standard

therapy

• ECOG PS 0 or 1

• ≥1 meas◆rable lesion

• PD-L1 positivitya

• No autoimmune

disease or interstitial

lung disease

aAt least 1% modified proportion score or interface pattern (QualTek IHC using 22C3 antibody clone).bIf SD or better when pembrolizumab discontin◆ed and s◆bseq◆ently ha❖e PD, patients may be eligible to res◆me pembroliz◆mab for ≥1 year.cIf clinically stable, patients are to remain on pembrolizumab until progressive disease is confirmed on a second scan performed ≥4 weeks later.

Mehnert J, ESMO 2017


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ASCO 2018 Poster session: Vijayvergia et al.

Pembrolizumab monotherapy in patients with previously

treated metastatic high grade neuroendocrine neoplasms


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CLOSING REMARKS

• Although many different treatments are available no

therapeutic sequence or integration has been validated so far

for tumor growth control

• Therefore GEP NET patients should be preferably managed

involving a NEN referral Centers with a NEN-dedicated MDT

• Predictive factors of response/efficacy are a urgent unmet

need


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European Institute of Oncology, IEO, Milan, Italy

ENETS Center of Excellence for GEP NETs


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Update on neuroendocrine tumors - OncologyPRO

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