ESMO 2016 abstracts

570 Pages·2016·7.34 MB·English

Annals of Oncology
Official Journal of the European Society for Medical Oncology and
the Japanese Society of Medical Oncology
editor-in-chief: editorsemeriti Preclinicalandexperimentalscience
T.U.E.Helleday,Stockholm,Sweden
J.-C. Soria, Villejuif, France F.Cavalli,Bellinzona,Switzerland
D.J.Kerr,Oxford,UK Precisionmedicine
associateeditors C.Swanton,London,UK
J.B.Vermorken,Edegem,Belgium
Bioinformatics
Urogenitaltumors Gynecologicaltumors
N.McGranahan,London,UK
G.Attard,Sutton,UK B.Monk,Phoenix,Arizona,USA
M.DeSantis,Birmingham,UK S.Pignata,Naples,Italy BioTechnologies
E.Mardis,St.Louis,Missouri,USA
Melanoma
Gastrointestinaltumors
D.Arnold,Lisbon,Portugal G.Long,Sydney,Australia Onco-Immunology
G.Coukos,Lausanne,Switzerland
A.Cervantes,Valencia,Spain Hematologicalmalignancies
A.Snyder,NewYork,NewYork,USA
J.Tabernero,Barcelona,Spain K.Tsukasaki,Kashiwa,Japan
P.L.Zinzani,Bologna,Italy Statistics
Breasttumors
F.André,Villejuif,France Supportivecare M.Buyse,Brussels,Belgium
K.Jordan,Halle,Germany
C.Sotiriou,Brussels,Belgium Molecularandsurgicalpathology
Epidemiology I.I.Wistuba,Houston,Texas,USA
Thoracictumors
P.Boffetta,NewYork,NewYork,USA
T.Mitsudomi,Osaka,Japan Annalsofoncologyonline
J.F.Vansteenkiste,Leuven,Belgium Sarcomaandclinicalpharmacology C.Ferté,Villejuif,France
O.Mir,Villejuif,France
Headandnecktumors Industrycorner:perspectivesandcontroversies
A.T.C.Chan,Shatin,HongKong Earlydrugdevelopment K.Dhingra,NewYork,NewYork,USA
E.Cohen,SanDiego,California,USA J.-C.Soria,Villejuif,France
editorial board
M.S.Aapro,Genolier,Switzerland R.Govindan,St.Louis,Missouri,USA A.Ohtsu,Chiba,Japan
Y.Ando,Nagoya,Japan P.Grimison,Sydney,Australia I.Okamoto,Fukuoka,Japan
P.Autier,Lyon,France A.Grothey,Rochester,Minnesota,USA S.I.Ou,Orange,California,USA
H.A.AzimJr,Marseille,France S.Halabi,Durham,NorthCarolina,USA X.Paoletti,Paris,France
I.Barnes,Oxford,UK D.G.Haller,Philadelphia,Pennsylvania,USA C.Pezaro,Melbourne,Australia
J.Baselga,NewYork,USA K.Hotta,Okayama,Japan P.Pfeiffer,Odense,Denmark
J.Bellmunt,Boston,Massachusetts,USA R.A.Huddart,Sutton,UK S.V.Porceddu,Brisbane,Australia
B.Besse,Villejuif,France I.Hyodo,Tsukuba,Japan M.R.Posner,NewYork,USA
J.Beyer,Zurich,Switzerland M.Ignatiadis,Brussels,Belgium S.Postel-Vinay,Villejuif,France
P.Bierman,Omaha,Nebraska,USA D.H.Ilson,NewYork,NewYork,USA A.Psyrri,NewHaven,Connecticut,USA
C.Bokemeyer,Hamburg,Germany H.Iwata,Aichi,Japan D.Quinn,LosAngeles,California,USA
N.Boku,Tokyo,Japan F.Janku,Houston,Texas,USA S.S.Ramalingam,Atlanta,Georgia,USA
F.Bretz,Basel,Switzerland N.Katsumata,Kawasaki,Japan M.Reck,Grosshansdorf,Germany
E.Bria,Verona,Italy N.Kiyota,Kobe,Japan B.Rini,Cleveland,Ohio,USA
E.F.Burgess,Charlotte,NorthCarolina,USA C.LaVecchia,Milan,Italy R.Rosell,Badalona,Spain
P.G.Casali,Milan,Italy P.N.JrLara,Sacramento,California,USA A.D.Roth,Geneva,Switzerland
F.Ciardiello,Naples,Italy S.Loi,Melbourne,Australia R.Salazar,Barcelona,Spain
A.Comandone,Turin,Italy S.Loibl,Neu-Isenburg,Germany M.Scartozzi,Ancona,Italy
P.G.Corrie,Cambridge,UK F.Lordick,Leipzig,Germany N.Schmitz,Hamburg,Germany
G.Curigliano,Milan,Italy Y.Loriot,Villejuif,France H.-J.Schmoll,Halle,Germany
A.DiLeo,Prato,Italy S.Lutzker,SanFrancisco,California,USA I.Sekine,Tsukuba,Japan
T.Dorff,LosAngeles,California,USA T.Macarulla,Barcelona,Spain Q.Shi,Rochester,Minnesota,USA
H.Dosaka-Akita,Sapporo,Japan M.Martin,Madrid,Spain A.F.Sobrero,Genoa,Italy
E.A.Eisenhauer,Kingston,Canada S.Matsui,Tokyo,Japan G.Sonpavde,Birmingham,Alabama,USA
A.Eniu,Cluj-Napoca,Romania J.Maurel,Barcelona,Spain S.Takahashi,Tokyo,Japan
T.Fenske,Milwaukee,Wisconsin,USA G.McArthur,Melbourne,Australia M.Toi,Kyoto,Japan
S.Galbraith,Cambridge,UK S.Michiels,Villejuif,France B.A.VanTine,St.Louis,Missouri,USA
G.Giamas,Brighton,UK H.Minami,Kobe,Japan E.Vilar,Houston,Texas,USA
R.Glynne-Jones,Northwood,UK Y.Nishimura,Osaka-Sayama,Japan Y.-L.Wu,Guangzhou,China
B.-C.Goh,Singapore,Singapore K.Nishio,Osaka-Sayama,Japan J.C.-H.Yang,Taipei,Taiwan
A.Goldhirsch,Milan,Italy M.Ogura,Gifu,Japan S.Yano,Kanazawa,Japan
executiveeditor:LewisRowett
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Annals of
Oncology
Official Journal of the European Society
for Medical Oncology and the Japanese
Society of Medical Oncology
Volume 27, 2016 Supplement 6
Abstract Book of the 41st ESMO Congress (ESMO 2016)
–
7 11October2016,Copenhagen,Denmark
Guest Editors:
ESMO 2016 Congress ScientificCommittee
Annals of Oncology
Official Journal of the European Society for
Medical Oncology and the Japanese Society of Medical Oncology
Volume 27, 2016 Supplement 6
Abstract Book of the 41st ESMO Congress (ESMO 2016)
–
Copenhagen, Denmark, 7 11 October 2016
AboutESMO vi_vi Healtheconomics vi351
ESMOExecutiveBoard vi_vi Immunotherapyofcancer vi359
ESMO2016CongressOfficers vi_vii Melanomaandotherskintumours vi379
Acknowledgements vi_x Newdiagnostics vi401
NSCLC,earlystage vi407
Submitted abstracts NSCLC,locallyadvanced vi411
BasicScience vi1 NSCLC,metastatic vi416
Biomarkers vi15 Palliativecare vi455
Breastcancer,earlystage vi43 Preventionandscreening vi462
Breastcancer,locallyadvancedandmetastatic vi68 Psycho-oncology vi469
Clinicaltrialsmethodology vi100 Publichealth vi474
CNStumours vi103 Sarcoma vi483
Developmentaltherapeutics vi114 SCLC vi493
Endocrineandneuroendocrinetumours vi136 Supportivecare vi497
Gastrointestinaltumours,colorectal vi149 Thoracicmalignancies,other vi522
Gastrointestinaltumours,non-colorectal vi207 Translationalresearch vi526
Genitourinarytumours,prostate vi243 Tumourbiologyandpathology vi545
Genitourinarytumours,non-prostate vi266 Late-BreakingAbstractsanddeferredpublication
Gynaecologicalcancers vi296 Drugindex vi552
HaematologicalMalignancies vi313 Translationalresearchindex vi556
Headandneckcancer vi328
Note:Abstractsuffixes
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“PD”indicatesasubmittedabstractacceptedforPosterDiscussion
“P”indicatesasubmittedabstractacceptedforPosterPresentation
“TiP”indicatesasubmittedabstractacceptedforPosterPresentation,TrialinProgress
__PRindicatesasubmittedabstractselectedforinclusionintheESMOPressProgramme
Volume27 |Supplement6| October2016
The European Society for Medical Oncology (ESMO)
ESMO istheleading professional organisation for medical oncology, withthe overarching goalof improving outcomes for
cancer patients everywhere. Wearethesocietyof reference foroncologyeducation andinformation, and arecommittedto
supporting ourmemberstodevelop andadvancein afast-evolvingprofessional environment.
Founded in1975, ESMO has European roots witha global reach: wewelcome oncology professionals from around the
world. Wearea home foralloncologystakeholders, connectingprofessionals withdiverse expertise and experience,
and speaking withone voice forourdiscipline. Oureducation and information resources support anintegrated
multi-professional approach to cancercare, froma medical oncologyperspective. We seekto erase boundaries incancer
care, whether betweencountries or specialities, and pursue our mission acrossoncology,worldwide.
The ESMO community bringstogether more than 13,000 oncologyprofessionals fromover 130 countries. Drawingon 40
years ofexperienceand around 500expert committee members, ESMO servesits members and theoncologycommunity
through:
• Post-graduate oncologyeducation and training
• Career development and leadership training for the next generations ofoncologists
• Internationalcongresses and workshopsto share expertiseand bestpractice, learnabout themost up-to-date scientific
advances,and connect withcolleaguesinrelated disciplines
• Continuously reviewed, evidence-based standards forcancercare inEurope
• Advocacyand consultation tofosterafavourable environment for scientific research
Cancercareis rapidly becoming moreintegrated andmorespecialised;whethertheir field is research, diagnosis, treatment,
care, oradvocacy, oncology professionals need toboth build their specialist knowledgeand connect with thebest
practitioners inother disciplines worldwide. ESMO membership makesthis possible.
Please visit esmo.org to learn more. Across Oncology.Worldwide.
ESMO Executive Board
President Fortunato Ciardiello, Naples, Italy
President-Elect Josep Tabernero, Barcelona, Spain
PastPresident and Membership Committee Chair RolfA. Stahel, Zurich, Switzerland
Treasurer Emile Voest, Amsterdam, The Netherlands
EducationalCommitteeChair Andrés Cervantes, Valencia,Spain
National Representatives and Membership Committee Chair FatimaCardoso, Lisbon,Portugal
EU PolicyCommittee Chair Paolo G. Casali, Milan, Italy
Global Policy Committee Chair Alexandru Eniu, Cluj-Napoca, Romania
Guidelines Working Group Chair George Pentheroudakis, Ioannina,Greece
Press and Media Affairs CommitteeChair Solange Peters, Lausanne, Switzerland
Practising Oncologists CommitteeChair Stefan Rauh, Esch-sur-Alzette, Luxembourg
Board Member Dirk Arnold, Lisbon,Portugal
Board Member Alexander M.M. Eggermont, Villejuif, France
Board Member Jacek Jassem, Gdansk, Poland
Board Member Christoph Zielinski, Vienna, Austria
ESMO 2016 Congress Officers
2016 ESMO and Congress President
FortunatoCiardiello,Naples, Italy
Scientific Committee Chair
Andrés Cervantes, Valencia, Spain
Educational Chair
Jean-Yves Douillard, Lugano, Switzerland
Press Officer
Solange Peters, Lausanne,Switzerland
LocalOfficer
UlrikN. Lassen, Copenhagen, Denmark
Scientific Committee
Basicscienceandtranslationalresearch Breastcancer,earlystage
Chair:RichardMarais,Manchester,UK Chair:MarcoColleoni,Milan,Italy
CatherineAlix-Panabieres,Montpellier,France HatemA.Azim,Jr.,Marseille,France
AntonBerns,Amsterdam,Netherlands JacquesBernier,Genolier,Switzerland
AlbertoBardelli,Candiolo,Italy HerveBonnefoi,Bordeaux,France
CarlosCaldas,Cambridge,UK KarenGelmon,Vancouver,BC,Canada
RaffaeleCalifano,Manchester,UK NadiaHarbeck,Munich,Germany
RobertGatenby,Tampa,FL,USA GuyJerusalem,Liege,Belgium
RamaswamyGovindan,St.Louis,MO,USA SybilleLoibl,Neu-Isenburg,Germany
DavidHuntsman,Vancouver,BC,Canada AleixPrat,Barcelona,Spain
ClareIsacke,London,UK IsabelT.Rubio,Barcelona,Spain
JoanSeoane,Barcelona,Spain ElżbietaSenkus-Konefka,Gdańsk,Poland
SheilaSingh,Hamilton,ON,Canada AndrewTutt,London,UK
ThomasTüting,Bonn,Germany GiuseppeViale,Milan,Italy
ChristofvonKalle,Heidelberg,Germany
Breastcancer,metastatic CNStumours
Chair:RobertE.Coleman,Sheffield,UK Chair:AlbaBrandes,Bologna,Italy
FabriceAndré,Villejuif,France CarmenBalaña,Barcelona,Spain
FatimaCardoso,Lisbon,Portugal DeborahBlumenthal,TelAviv,Israel
PierFrancoConte,Padua,Italy MichaelBrada,Bebington,UK
JavierCortes,Barcelona,Spain RogerHenriksson,Stockholm,Sweden
LuisCosta,Lisbon,Portugal SimoneNiclou,Luxembourg
RogerGomis,Barcelona,Spain GuidoReifenberger,Dusseldorf,Germany
NadiaHarbeck,Munich,Germany MarcSanson,Paris,France
PerKarlsson,Gothenburg,Sweden ColinWatts,Cambridge,UK
ShereneLoi,Melbourne,Australia MichaelWeller,Zurich,Switzerland
PeterSchmid,London,UK PatrickWen,Boston,MA,USA
DavidWarr,Toronto,ON,Canada
Developmentaltherapeutics Gastrointestinaltumours,colorectal
Chair:JordiRodón,Barcelona,Spain Chair:JulienTaieb,Paris,France
UdaiBanerji,Sutton,UK RichardAdams,Cardiff,UK
MarkBasik,Montreal,QC,Canada DirkArnold,Lisbon,Portugal
IreneBraña,Barcelona,Spain DanielaAust,Dresden,Germany
MarioCampone,SaintHerblain,France ChiaraCremolini,Pisa,Italy
BryanHennessy,Dublin,Ireland ThomasGruenberger,Vienna,Austria
Chia-ChiLin,Taipei,Taiwan VolkerHeinemann,Munich,Germany
ChristopheMassard,Villejuif,France FlorenceHuguet,Paris,France
PaoloNuciforo,Barcelona,Spain Claus-HenningKoehne,Oldenburg,Germany
ChristianRolfo,Edegem,Belgium FotiosLoupakis,Pisa,Italy
JanSchellens,Amsterdam,Netherlands RamonSalazar,L’HospitaletdeLlobergat,Spain
ChristopherTwelves,Leeds,UK SabineTejpar,Leuven,Belgium
ChristopheTournigand,Creteil,France
Gastrointestinaltumours,non-colorectal Genitourinarytumours,prostate
Chair:FlorianLordick,Leipzig,Germany Chair:GerhardtAttard,Sutton,UK
FátimaCarneiro,Porto,Portugal HimishaBeltran,NewYork,NY,USA
IanChau,Sutton,UK JohanndeBono,London,UK
EduardoDiazRubio,Madrid,Spain RonalddeWit,Rotterdam,Netherlands
MichelDucreux,Villejuif,France EleniEfstathiou,Houston,TX,USA
AxelHillmer,Mainz,Germany FelixFeng,AnnArbor,MI,USA
YelenaJanjigian,NewYork,NY,USA SilkeGillessen,St.Gallen,Switzerland
ChristopheMariette,Lille,France AxelHeidenreich,Aachen,Germany
PerPfeiffer,Odense,Denmark YohannLoriot,Villejuif,France
FernandoRivera,Santander,Spain DavidOlmos,Madrid,Spain
ArnaudRoth,Geneva,Switzerland StephaneOudard,Paris,France
EricVanCutsem,Leuven,Belgium MathewSydes,London,UK
MarcelVerheij,Amsterdam,Netherlands ScottTomlins,AnnArbor,MI,USA
Genitourinarytumours,non-prostate Gynaecologicalcancers
Chair:JoaquimBellmunt,Boston,MA,USA Chair:SandroPignata,Naples,Italy
LaurenceAlbiges,Villejuif,France CarienL.Creutzberg,Leiden,Netherlands
FerranAlgaba,Barcelona,Spain AntonioGonzález-Martín,Madrid,Spain
ArisBamias,Athens,Greece CharlieGourley,Edinburgh,UK
AxelBex,Amsterdam,Netherlands FlorenceJoly,Caen,France
BernardEscudier,Villejuif,France JonathanLedermann,London,UK
ViktorGrünwald,Hannover,Germany DomenicaLorusso,Milan,Italy
ChristianKollmannsberger,Vancouver,BC,Canada MansoorMirza,Copenhagen,Denmark
AntonioLópez-Beltran,Lisbon,Portugal AndresPoveda,Valencia,Spain
NicholasMottet,St.Etienne,France IsabelleRay-Coquard,Lyon,France
AndreaNecchi,Milan,Italy CristianaSessa,Bellinzona,Switzerland
JackSchalken,Nijmegen,Netherlands IgnaceVergote,Leuven,Belgium
ManuelaSchmidinger,Vienna,Austria
Haematologicalmalignancies Headandneckcancer
Chair:ChristianBuske,Ulm,Germany Chair:AmandaPsyrri,Athens,Greece
PeterCampbell,Hinxton,UK AnaCastro,Porto,Portugal
AndrésFerreri,Milan,Italy SandrineFaivre,Clichy,France
RamonGarcia-Sanz,Salamanca,Spain VincentGregoire,Brussels,Belgium
PaoloGhia,Milan,Italy NikolaosKavantzas,Athens,Greece
KlausHerfarth,Heidelberg,Germany LisaLicitra,Milan,Italy
PeterJohnson,Southampton,UK Jean-PascalMachiels,Brussels,Belgium
MarcoLadetto,Alessandria,Italy MarcoMerlano,Cuneo,Italy
StevenLeGouill,Nantes,France RicardMesía,L’HospitaletdeLlobregat,Spain
ArmandoLopez-Guillermo,Barcelona,Spain PieroNicolai,Brescia,Italy
GertJ.Ossenkoppele,Amsterdam,Netherlands ChristosPerisanidis,Vienna,Austria
MarianoProvencio,Madrid,Spain MassimoTommasino,Lyon,France
EvangelosTerpos,Athens,Greece
Immunotherapyofcancer Melanomaandotherskintumours
Chair:JohnHaanen,Amsterdam,Netherlands Chair:OlivierMichielin,Lausanne,Switzerland
PhilippBeckhove,Heidelberg,Germany PaoloAscierto,Naples,Italy
MarioColombo,Milan,Italy BorisC.Bastian,SanFrancisco,CA,USA
JérômeGalon,Paris,France ReinhardDummer,Zurich,Switzerland
IgnacioMelero,Pamplona,Spain Jean-JacquesGrob,Marseille,France
PaulNathan,Northwood,UK AxelHauschild,Kiel,Germany
UlfPetrausch,Zurich,Switzerland ChristophHoeller,Vienna,Austria
ThomasPowles,London,UK PaulLorigan,Manchester,UK
SuzyScholl,Paris,France JosepMalvehy,Barcelona,Spain
IngeMarieSvane,Herlev,Denmark CarolineRobert,Villejuif,France
SjoerdvanderBurg,Leiden,Netherlands BenoîtVandenEynde,Brussels,Belgium
LaurenceZitvogel,Villejuif,France JeffreyWeber,NewYork,NY,USA
NETsandendocrinetumours Non-metastaticNSCLCandotherthoracicmalignancies
Chair:RocioGarcia-Carbonero,Madrid,Spain Chair:DirkDeRuysscher,Maastricht,Netherlands
JaumeCapdevila,Barcelona,Spain PaulBaas,Amsterdam,Netherlands
MichelDucreux,Villejuif,France BenjaminBesse,Villejuif,France
MassimoFalconi,Milan,Italy Anne-MarieDingemans,Maastricht,Netherlands
DikKwekkeboom,Rotterdam,Netherlands WilfriedEberhardt,Essen,Germany
KjellÖberg,Uppsala,Sweden PilarGarrido,Madrid,Spain
MariannePavel,Berlin,Germany TetsuyaMitsudomi,Osaka-Sayama,Japan
GeorgePentheroudakis,Athens,Greece SanjayPopat,London,UK
EricRaymond,Lausanne,Switzerland JensBennSoerensen,Copenhagen,Denmark
GuidoRindi,Rome,Italy EstherTroost,Dresden,Germany
MercedesRobledo,Madrid,Spain JohanVansteenkiste,Leuven,Belgium
JuanValle,Manchester,UK GiuliaVeronesi,Milan,Italy
JamesYao,Houston,TX,USA
NSCLC,metastatic Publichealthandhealtheconomics
Chair:EgbertSmit,Amsterdam,Netherlands Chair:RosaGiuliani,Rome,Italy
FabriceBarlesi,Marseille,France TitAlbreht,Ljubljana,Slovenia
FionaBlackhall,Manchester,UK PeterBoyle,Ecully,France
RafalDziadziuszko,Gdansk,Poland PaoloG.Casali,Milan,Italy
StephenFinn,Dublin,Ireland JackCuzick,London,UK
KeithKerr,Aberdeen,UK SilviadeSanjosé,L’HospitaletdeLlobregat,Spain
PeterMeldgaard,Aarhus,Denmark HarrydeKoning,Rotterdam,Netherlands
TonyS.K.Mok,HongKong,China AlexEniu,Cluj-Napoca,Romania
SilviaNovello,Orbassano,Italy ValerieLemmens,Eindhoven,Netherlands
LuisPaz-Ares,Madrid,Spain AlbertoOcana,Albacete,Spain
SolangePeters,Lausanne,Switzerland RichardSullivan,London,UK
MartinReck,Grosshansdorf,Germany AndreasUllrich,Geneva,Switzerland
GregoryJ.Riely,NewYork,NY,USA
Sarcoma Supportiveandpalliativecare
Chair:OlivierMir,Villejuif,France Chair:KarinJordan,Halle,Germany
StefanBielack,Stuttgart,Germany MattiAapro,Genolier,Switzerland
JeanYvesBlay,Lyon,France MarieFallon,Edinburgh,UK
PhilippeCassier,Lyon,France PetraFeyer,Berlin,Germany
A.PaoloDeiTos,Treviso,Italy JoernHerrstedt,Odense,Denmark
XavierGarciadelMuro,Barcelona,Spain SteinKaasa,Trondheim,Norway
AlessandroGronchi,Milan,Italy BernardoRapoport,Johannesburg,SouthAfrica
RobinJones,London,UK CarlaRipamonti,Milan,Italy
CecileLePechoux,Villejuif,France FaustoRoila,Terni,Italy
JavierMartinBroto,Seville,Spain TiinaSaarto,Helsinki,Finland
SilviaStacchiotti,Milan,Italy FlorianScotté,Paris,France
MaudToulmonde,Bordeaux,France FlorianStrasser,St.Gallen,Switzerland
WinettevanderGraaf,London,UK
The European Society for MedicalOncology wishestoexpress its appreciation and gratitude to allof theaboveexperts for
theirmajoreffort in reviewing and selecting thecontent ofthis AbstractBook.

AnnalsofOncology27(Supplement6):vi1–vi14,2016
doi:10.1093/annonc/mdw362
basicscience detectedbyELISAorqPCR,respectively.WeconductedaBioMaphumancell
co-culturesystemanalysiswithperipheralbloodmononuclearcells,endothelialcells,
andH1299humanlungcancercellstoevaluateeffectsofeachsingleagentand
combinationtreatmentsonTh1/Th2immuneresponse.
1O EPHA2blockadeovercomesprimaryandacquiredresistanceto Results:CombinationofLENwithPD-1mAbshowedmorepotentinhibitoryactivity
anti-epidermalgrowthfactorreceptor(EGFR)therapyin againsttumorgrowthinall3modelscomparedwitheachsingleagent.Notably,
metastaticcolorectalcancer(mCRC) completetumorregressionsweredetectedinsomemicewithcombinationtreatmentin
theH22syngeneicmousetumormodel.Re-inoculationoffreshH22cellsintothese
G.Martini1,V.Belli2,P.P.Vitiello1,T.Troiani1,C.Cardone1,S.Napolitano1, curedmicewasrejected.BioMapanalysisshowedthatPD-1mAbincreasedbothTh1
V.Desiderio3,V.Sforza1,M.L.Ferrara1,G.Papaccio3,L.Mele3,G.Liguori4, andTh2cytokines,LENdecreasedTh2cytokines,andcombinationtreatment
G.Botti5,R.Franco6,F.Morgillo1,F.Ciardiello1,E.Martinelli1 increasedTh1cytokinesbutdecreasedTh2cytokines.ELISAandqPCRanalysisalso
1MedicalOncology,AOUSecondaUniversitàdegliStudidiNapoli(AOU-SUN), showedthatTh1cytokineswereincreasedbutTh2cytokinesweredecreasedwith
Naples,Italy,2DipartimentoMedico-ChirurgicodiInternisticaClinicae combinationtreatmentsintheLL/2andCT26syngeneicmousemodels.
sperimentale,AOUSecondaUniversitàdegliStudidiNapoli(AOU-SUN),Naples, Conclusions:TheresultsindicatethatthecombinationofLENwithPD-1mAbwas
Italy,3Istology,AOUSecondaUniversitàdegliStudidiNapoli(AOU-SUN),Naples, moreeffectivethansingle-agenttreatmentinmultiplesyngeneictumormodelsand
Italy,4AnatomiaPatologica,IstitutoNazionaleTumori–I.R.C.C.S-Fondazione wasaccompaniedwithapotentantitumorimmuneresponse.
Pascale,Naples,Italy,5Dipartimentodianatomiapatologica,IstitutoNazionale Legalentityresponsibleforthestudy:EisaiInc.
Tumori–I.R.C.C.S-FondazionePascale,Naples,Italy,6Anatomiapatologica,
Funding:EisaiInc.
AOUSecondaUniversitàdegliStudidiNapoli(AOU-SUN),Naples,Italy
Disclosure:Y.Kato,K.Tabata,Y.Hori,S.Tachino,Y.Funahashi,J.Matsui:Employee
ofEisaiCo.,Ltd.X.Bao,S.Macgrath,M.Matijevici:EmployeeofEisaiInc.
Background:EPHA2tyrosinekinasereceptorisimplicatedintumorprogression,
neovascularizationandmigrationinawiderangeofcancers.Westudieditsroleasa
potentialmarkerofresistancetoanti-EGFRdrugsincolorectalcancer(CRC).
3P DissectingtherolesofFraproteinsinlungadenocarcinoma
Methods:WeevaluatedtheexpressionandactivationofEPHA2inapanelofCRCcell
linessensitive(GEOandSW48cells)andresistant(HCT116,SW620,LOVO,SW480, A.Alfraidi1,L.Bakiri1,A.Ucero1,M.Musteanu2,M.Barbacid2,E.Wagner1
HCT15,SW48-CR[acquiredcetuximabresistant],GEO-CR)toanti-EGFRdrugsby 1Genes,DevelopmentandDisease,CNIO-SpanishNationalCancerCenter,
WesternBlot(WB)analysis.TheeffectofALW-II-41-27(EPHA2inhibitor)and/or Madrid,Spain,2MolecularOncology,CNIO-SpanishNationalCancerCenter,
cetuximaboncellsurvivalanddrugsensitivitywasevaluatedbyMTTassay.Apoptosis Madrid,Spain
andcellcycleanalysiswereanalysedbyflowcytometry.SW48-CRsubcutaneous
xenograftmodelswereusedforinvivoexperiments.EPHA2expressionwasassessed
byimmunohistochemistry(IHC)inmCRCtumors. Background:Lungcancerisalife-threateningdiseasewithincreasedincidence
worldwide.Mostpatientsarediagnosedwithadvanceddisease,andasaresult,the5year
Results:EPHA2wasdifferentlyactivatedamongcelllineswithhighlevelsof
survivalrateisamongthelowestincancer.Amongalllungcancer,85%arenonsmall
phosphorylationinHCT116,SW620,LOVO,GEO-CRandSW48-CRcells.CRCcell
lungcancer(NSCLC)subtype,whichcanbesubdividedinlungadenocarcinoma(ADC)
linesweredifferentlysensitivetoALW-II-41-27withanIC50rangingfrom0.05to2 andsquamouscellcarcinoma(SCC).K-RasmutationisthemostcommoninNSCLC,
mM(beingHCT116,SW620,LOVO,SW48-CR,HCT15,GEOthemostsensitive
butnodrugsthattargetK-Rasdirectlyorindirectlyhaveyetbeendiscovered.Therefore,
whereasGEO-CRandSW48themostresistant).WecombinedALW-II-41-27plus
thereisaneedtofindadruggabletargetthatcanhelpinthetreatmentoflungcancer
cetuximab,todemonstrateifEPHA2inhibitionmightrevertprimaryandacquired
patients.Fos-relatedantigen2(Fra-2),amemberofAP-1transcriptionfactors,hasbeen s
resistancetocetuximab.Combinedtreatmentinducedasynergisticanti-proliferative showntobeactivatedbyK-Rassignalling,aswellasderegulatedinmanycancertypes. ct
andapoptoticeffectsincellswitheitherprimary(HCT15)andacquired(GEO-CR, a
ScpoWMnA4fi8rPm-KCeRadn)bdryepstiAhsteKarnTec.deCutecoltlicocenytcuolxefimpanEaaPblHy.sTAish2edlesemyvneoelsnrgsatinrsdatitceadamcGtai2vrkipteyhdoalysfetihnaehrricebositmtiwobniitnhoaftthiaocentivwaatesd Mtsroafenttwshcaorrdieps.t:WoPmeroigcgednnaoetsraiastfervodamlaueg1eo9n2fe8FtriNca-Se2CnmgLiCnReNpearAetideenxmptsoretuhsssreioomungolhedvaeenll(woGnaElsiMnaesMsseu)ssrfeovdirvFianrlaa-n2alysis abstr
combinationcomparedwithALWII-41-27alone.TheinvivoexperimentofSW48-CR inactivationinanexperimentalmodeloflungADCinducedbyK-Rasmutation(G12V)
subcutaneousxenograftmodelsandtheEPHA2expressionbyIHCofmCRCtumors andp53inactivation.Fra-2andp53inactivation,andmutantK-Rasexpression,are
patientstreatedwithantiEGFRtherapyarecurrentlyongoingandwillbepresented. inducedsimultaneouslybyinfectionwithaCre-expressingAdenovirusdelivered
intra-nasally.Developmentoflungtumourswaslongitudinallymonitoredbymicro-CT.
Conclusions:AselectiveEPHA2inhibitorisabletorevertinvitroprimaryand
acquiredresistancetoanti-EGFRtherapy,highlightingEPHA2asapotential Results:Fra-2mRNAhighexpressionwasfoundtobesignificantlycorrelatedtopoor
therapeutictargetinmCRCtreatment. outcomeinthisADCpatientcohort.GeneticinactivationofFra-2inthislungcancer
modelprolongsthesurvivalofthemicecomparedwithheterozygousFra-2by
Legalentityresponsibleforthestudy:SecondUniversityofNaples
decreasingtumorincidence,numberandvolume.
Funding:AIRC
Conclusions:OurresultsidentifyanewpotentialtherapeutictargetinK-Rasmutated
Disclosure:Allauthorshavedeclarednoconflictsofinterest. lungADC.
Legalentityresponsibleforthestudy:A.Alfraidi
2PD Lenvatinibmesilate(LEN)enhancedantitumoractivityofa Funding:WorldWideCancerResearchformerlyAICR
PD-1blockadeagentbypotentiatingTh1immuneresponse Disclosure:Allauthorshavedeclarednoconflictsofinterest.
Y.Kato1,X.Bao2,S.Macgrath2,K.Tabata1,Y.Hori1,S.Tachino1,M.Matijevici2,
Y.Funahashi1,J.Matsui1 4P Metallothionein1Hfunctionsasatumorsuppressorin
1EisaiCo.,Ltd.,Ibaraki,Japan,2Eisai,Inc,Andover,MA,USA hepatocellularcarcinoma
Background:LENselectivelyinhibitsthekinaseactivityofVEGFR1-3,FGFR1-4,KIT, Y.Zheng1,L.Jiang2,N.Xu1,C.Xiao1,Y.Hu3,X.Wang1,L.Chen4,H.Fang5,
PDGFRα,andRET,whichareinvolvedintumorangiogenesisandproliferationin J.Zhu6
severalcancertypes.Currently,Phase1b/2clinicaltrialsofthecombinationofLEN 1DepartmentofMedicalOncology,1stAffiliatedHospitalofZhejiangUniversity
andpembrolizumab(amonoclonalantibody[mAb]thatblockstheinteraction SchoolofMedicine,Hangzhou,China,2DepartmentofNeurology,TheChildren’s
betweenPD-1anditsligands)areongoingforselectedtypesofcancerincluding Hospital,ZhejiangUniversitySchoolofMedicine,Hangzhou,China,3Department
melanomaandrenalcancer.Inordertounderstandtheantitumoreffectand ofHaematology,1stAffiliatedHospitalofZhejiangUniversitySchoolofMedicine,
mechanismofactionofthecombinationofLENandPD-1blockadetreatment,we Hangzhou,China,4DepartmentofMedicalOncology,1stPeople’sHospitalof
analyzedimmuneresponseinsyngeneicmurinetumormodels. Taizhou,Taizhou,China,5DepartmentofOncologyCancerCenter,Zhejiang
XiaoshanHospital,Hangzhou,China,6MedicalOncology,HangzhouCancer
Methods:WeexaminedantitumoractivityofcombinationtreatmentofLEN(10mg/
Hospital,Hangzhou,China
kg,qd)andanti-mousePD-1mAb(500µg/mouse,twiceweekly)againstLL/2murine
lungcarcinoma,H22murinehepatocellularcarcinoma,andCT26murinecoloncancer
insyngeneicmousemodels.Forimmunepopulationanalyses,tumororspleensamples Background:Hepatocellularcarcinoma(HCC)remainsamajorcauseofcancer-related
wereanalyzedbyflowcytometry.Theexpressionofsolublefactorsandgeneswas deathworldwide.Metallothioneins(MTs)arelow-molecularweight,cysteine-rich
©EuropeanSocietyforMedicalOncology2016.PublishedbyOxfordUniversityPressonbehalfoftheEuropeanSocietyforMedicalOncology.
Allrightsreserved.Forpermissions,pleaseemail:[email protected].