File Download

There are no files associated with this item.

  Links for fulltext
     (May Require Subscription)
Supplementary

Article: Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial

TitleNeratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial
Authors
Martin, MiguelHolmes, Frankie A.Ejlertsen, BentDelaloge, SuzetteMoy, BeverlyIwata, Hirojivon Minckwitz, GunterChia, Stephen K.L.Mansi, JanineBarrios, Carlos H.Gnant, MichaelTomašević, ZoricaDenduluri, NeelimaŠeparović, RobertGokmen, ErhanBashford, AnnaRuiz Borrego, ManuelKim, Sung BaeJakobsen, Erik HuggerCiceniene, AudroneInoue, KenichiOverkamp, FriedrichHeijns, Joan B.Armstrong, Anne C.Link, John S.Joy, Anil AbrahamBryce, RichardWong, AlvinMoran, SusanYao, BinXu, FengAuerbach, AlanBuyse, MarcChan, ArleneHarvey, VernonTomek, RudolfRobert, Nicholas J.Gore, IraSmith, John W.Masuda, NorikazuDi Sean Kendall, S.Harker, William GraydonPetrakova, KatarinaGuerrero Zotano, AngelSimon, Amparo RuizKonstantinovic, Zora NeskovicIannotti, Nicholas O.Tassone, PierfrancescoRodriguez, Gladys I.Jáñez Martinez, NoeliaCrespo Massieu, CarmenSmickoska, SnezanaSomali, IsilYilmaz, UgurAlonso, Mirta GarciaRosales, Adolfo MuriasCold, SoerenKnoop, Ann SoegaardPatt, DebraHellerstedt, Beth A.Morales Murillo, SerafinMayer, Ingrid A.Means-Powell, Julie AnnHui, RinaSenecal, Francis M.Shen, ZhenzhouLuczak, Adam AndrzejChui, Joanna W.Y.Tsang, Janice Wing hangLang, IstvanRai, YoshiakiHozumi, YasuoTen Tije, Albert J.Bhandari, ManishOsborne, Cynthia R.C.Ohtani, ShoichiroHigaki, KenjiWatanabe, KenichiTaguchi, KazunoriTakahashi, MasatoFilipovic, SladjanaHansen, Vincent L.Rao, Vijayarama PhooshkooruGupta, ManishPetrov, PetarCoudert, BrunoVojnovic, ZeljkoPolya, ZsofiaMiyaki, ToshikoYamamoto, NaohitoBrincat, StephenLesniewski-Kmak, KrzysztofChmielowska, EwaBirhiray, Ruemu E.Citron, Marc L.Papish, Steven WilliamBerry, William R.Langkjer, Sven TygeGarcia Sáenz, José AngelArance, Ana MariaEfrat, NoaSarosiek, TomaszGrzeda, LukaszManalo, YvonneSmith, Julie C.Vaziri, IrfanHealey, TabithaRahim, YasminLuk, CynthiaDingle, BrianFranco, SandraSorensen, Peter GrundtvigAnand, AnjanaKhan, SarahFountzilas, GeorgeAogi, KenjiroShimizu, SatoruMikulova, MiladaSpanik, StanislavSomer, Robert A.Flynn, Patrick J.Coward, JermaineMainwaring, PaulJerusalem, GuySegura-Ojezzar, CarineLevy, ChristelleDelozier, ThierryKhayat, DavidColeman, Robert E.Rolles, Martin J.Maisano, RobertNardi, MarioIto, YoshinoriYumuk, Perran FuldenBasaran, GulSerdar Turhal, NazimWilkinson, Mary J.Green, Nathan B.Sidrys, Algis P.Hallmeyer, SigrunTestori, Douglas J.Sridhar, SrikalaChang, JoseSun, QiangJara-Sanchez, CarlosRubio, XabierGarrido, Maria LomasDe La Haba Rodriguez, Juan RafaelPerello Martorell, AntoniaAvelia Mestre, AntoniRifa Ferrer, Juliodel Barco Berron, SoniaNagy, ZsuzsannaTanaka, MakiIm, Young HyuckCarroll, Robert R.Dickerson, Laura C.Mace, Joseph R.Rivera, RageneKlein, Leonard M.Ruxer, RobertWilks, Sharon T.Kotasek, DusanPopov, VasilTaskova, ViolinaMarinova-Venkova, VioletkaTimcheva, ConstantaDesbiens, ChristineAyoub, Jean PierreGrenier, DebjaniMarschner, NorbertTesch, HansLueck, Hans JoachimJanssen, JanSchwaner, IngoWahlstrom, StineBrix, Eva HarderVallentin, SusanneKristensen, DanAndreeva, AnnaGlavicic, VesnaCalvo Plaza, IsabelAnton Torres, AntonioVeyret, CorinneBergerat, Jean PierreBourbouloux, EmmanuelleElla, Wendy AnnAlgurafi, HafizRobinson, AnneKim, Seung JinTaguchi, TetsuyaJuozaityte, ElonaMadretsma, StanleyRadema, SandraCzerniawska-Meier, MalgorzataRogowski, WojciechWagnerova, MariaRichards, Donald A.Tan-Chiu, ElizabethVasileios, AsskikisHenderson, Charles ArthurHolden, Viran RogerWang, XiaojiaTong, ZhongshengYang, JunlanGonzalez, Manuel EnriqueRezai, MahdiHackmann, Johnde Dueñas, Eduardo Martinezde las Heras, Begoña BermejoDourthe, Louis MarieChocteau-Bouju, DorotheeBougnoux, PhilippeKakolyris, StylianosKalofonos, HaralabosPectasidis, DimitriosNg, Ting YingPajkos, GaborSomogyine, Eva EzerTonini, GiuseppeGiuffrida, DarioTakao, ShintaroIshitobi, MakotoInaji, HideoTokuda, YutakaWozniak, KatarzynaLungulescu, DanLu, Yen ShenChang, King JenHill, JulianCroot, Christopher CharlesDekker, AlbertBelman, Neil D.Conde, MiguelMichaelson, Richard A.Kemmer, KathleenChui, StephenLuoh, Shiuh WenNahum, KennethGreenspan, Andrew R.Nichols, Joni C.Encarnacion, Carlos A.Niederman, Thomas M.J.Lee, TheresaAlexander, RolandGordon, RobertTomova, AntoanetRauch, DanielPopescu, Razvan AndreiRojas, Gustavo AdolfoVanasek, JaroslavNeunhoeffer, TanjaBarinoff, JanaGraffunder, GerdWolfgang, AbenhardtBojko, PeterHeinrich, Bernhardvon der Assen, AlbertAntonovic, Bogovic JurijAdrian, LeneRamos Vazquez, ManuelGonzalez Santiago, SantiagoDieras, VeroniqueBishop, Jill MerciaPerren, Timothy JohnVarthalitis, IoannisMavroudis, DimitrisGeorgoulias, VassilisChow, Louis W.C.Yau, Chung Cheung ThomasLiang, Raymond Hin SuenPikó, BélaWéber, AgnesKaufman, BellaDrumea, KarenDe Matteis, AndreaNuzzo, FrancescoCarteni, GiacomoTokunaga, ErikoIshida, MayumiOhno, ShinjiSato, NobuakiKuroi, KatsumasaNishimura, ReikiWatanabe, JunichiroChoi, Yoon JiPark, Kyong HwaWojtukiewicz, MarekJassem, JacekLoman, NiklasAskoy, SercanAltundag, Mustafa KadriSaip, PinarAli, Muhammad AmjadWade, James LloydChien, Amy JoBrandt, DebraNovik, YelenaJani, ChiragRice, Robert L.Gaffar, Yousuf A.R.Keaton, Mark R.Bajaj, RajeshKimmick, GretchenCampbell, DavidDe Boer, Richard HendryTurnquest, TheodoreLucas, SiderasDube, PierreXu, BingheSchilling, JoergApel, KlausSorensen, Peter GrundtvigVestlev, Peter MichaelJensen, Brita BjerregaardHaahr, VeraLescure, Alvaro RodriguezGrana Suarez, BegonaSaura Manich, CristinaJacquin, Jean PhilippeSamreen, AhmedBoiangiu, IonDank, MagdolnaFalci, CristinaJirillo, AntonioCinieri, SaverioUeno, TakayukiSato, FumiakiYamashiro, HiroyasuSugie, TomoharuLee, Keun SeokRo, Jung SilPark, In HaeBustam, Anita ZarinaSuszko-Kazarnowicz, MalgorzataPiktel, ArturKrzemieniecki, KrzysztofIorga, Polizenia GeorgetaYap, Yoon SimKakalejcik, MarianSevinc, AlperOzguroglu, MustafaChen, Shin ChehGreenberg, Richard H.Eisemann, Allan DanielDroder, RobertAbbasi, M. RashidVaysburd, MarinaCaldera, Humberto JoseHaley, Barbara BacsikRobin, ErwinInhorn, Roger C.Hufnagel, DavidKenyon, Peter D.Spremulli, EllenSilverman, PaulaJain, SharadWeigand, RobertMebis, JeroenKoynova, TatyanaLesperance, BernardPrausova, JanaKohne, Claus HenningSchneeweiss, AndreasJackisch, ChristianFuxius, StefanCubedo Cervera, RicardoUrruticoechea Ribate, AnderPernas Simon, SoniaValero Gallego, JoseArcusa Lanza, Angelsdel Pilar Alvarez, MariaFlorian Gerico, JesusCany, LaurentStebbing, JustinLabudovic, DejanGugic, DamirVrbanec, DamirRoila, FaustoBarni, SandroBidoli, PaoloMukai, HirofumiBermudez, VanessaEniu, AlexandruMirtsching, Barry C.Ibrahim, EmadTrey, JoanHergenroeder, Paul FrancisMahmood, AftabGonzalez, AnnelieseKaplan, Edward H.Ban, StacyPatel, DhimantClowney, BillyHoelzer, KarenSchwartz, Garry H.Salkeni, MohamedAbraham, JameNarula, SunilJabboury, KhaledMocharnuk, Robert ScottMcDonough, Richard H.Sikes, David H.Kawanchi, Ronald H.Schlabach, LarryMcCachren, Samuel SpenceCosgriff, Thomas M.Dreisbach, LukeDeMichele, AngelaPawl, LawrenceLucas, JenniferShinn, Lowell C.Alkhouri, NabielMonga, ManishLindquist, Deborah L.Anderson, Thomas C.Khurshid, HumeraWitherby, SabrinaErickson, NicholetteTraynor, AnnBose, RonPluard, Timothy J.Jones, Michael C.Prakash, SucharuVolterra, FabioCapo, GerardoFlaherty, Lawrence E.Gartner, ElainaBaidas, SaidOkazaki, IanNguyen, BichlienRakowski, ThomasOliff, IraLeach, Joseph W.Anderson, DanielKubiak, KendraTsai, MichaelaVroman, PhilippeDeleu, InesLybaert, WillemBorms, MarleenCouture, FelixWilson, Jonathan J.Hunt, GordonHolland, David R.Mingrone, WalterWang, ShusenLiu, DonggengJiang, ZefeiBenesova, VeraSmakal, MartinGarnolova, PetraVesper, Anne SophieNeumann, MonikaJanni, WolfgangLiedtke, CorneliaFischer, DorotheaGrischke, Eva MariaSeeger, DietmarMoebus, VolkerPrechtl, AnitaCarlos Camara Toral, JuanSanchez Munoz, AlfonsoGonzalez Jimenez, SoniaCassinello Espinosa, JavierCirauqui, BeatrizMargeli Vila, MireiaBatista Lopez, NorbertoChacon Lopez-Muniz, Jose Ignaciode la Cruz Mora, Miguel AngelMailliez, AudreyVanlemmens, LaurencePouessel, DamienEspie, MarcConibear, JohnRoylance, RebeccaHarnett, AdrianGeffen, DavidRuggeri, Enzo MariaGamucci, TeresaVan Groeningen, Cees J.Banas, RenataAlkis, NecatiHou, Ming FengKrie, Amy K.Vrindavanam, Nandagopal S.Howard, Orion M.Citrin, DennisMorginstin, Mark S.Desai, AjitSanchez, Ines J.Nixon, David AllenBeatty, Patrick G.Edmiston, KathrynMcLaughlin, MarilynEneman, Jonathan D.Lynch, Cynthia A.O'Brien, EdwardCall, Justin A.Lanier, Keith S.Conlin, AlisonBrooks, Donald J.McIntyre, KristiSaltzman, Marc A.Castine, Michael J.Ortega, Gregory L.Choi, Young M.Reynolds, Craig H.Brescia, Frankie AnnKramer, RitaKohn, Aimee D.Micha, John P.Rhee, Jessica M.Shah, SatishRiseberg, David A.Patterson, William KevinSalmon, Jean PaulAndre, ChantalBols, AlainD'hondt, RandalLuce, SylvieNouwynck, ClairePelgrims, GinoRichard, VincentVerschuere, JohanGeldhof, KurtCaspar, ClemensLuo, RongchengBednarik, OtakarSchwedler, KathrinSchmidt, MarcusNeumeister, RomyBischoff, JoachimRack, BrigitteRepp, RolandFries, StefanAdrion, RalfSchulz, VolkerKlare, PeterDanei, MahmoudOssenbuhl, DirkKusche, Jakob ManfredGriesinger, FrankBaena Canada, Jose ManuelMartinez del Prado, PurificacionMachover, DavidMayeur, DidierTrufflandier, NathalieDelecroix, ValerieMousseau, MireilleMouret-Reynier, Marie AngeNabholtz, Jean MarcChetiyawardana, Anula D.Papandreou, ChristosHornyak, LajosFaluhelyi, ZsoltSimo, ErzsebetDi Palma, MarioCognetti, FrancescoGorzegno, GabriellaDogliotti, LuigiGridelli, CesareFalcone, AlfredoSoto Parra, HectorBuscarino, CalogeroIm, Seock AhSanchez Llamas, BenitoDercksen, WouterErdkamp, FranciscusRuit, Jan B.Braun, HansPortielje, Joanneke E.A.Ciltas, AydinBuyukberber, SuleymanBenekli, MustafaZahalsky, Andrew J.Jaslow, RebeccaThomas, Gary W.Maini, ArchanaWiznitzer, IsraelKhojasteh, AliFrancisco Gonzalez, ManuelKong, Lynn R.Padmanabhan, ArunaConkright, William A.Swain, Sandra M.Faig, Douglas E.Jain, KirtiYanagihara, Ronald H.Ottaviano, YvonneDelmas, AndrewSteele, Heather A.Rainey, Gordon K.Harris, Penelope J.Burris, Jason K.Rupard, Erik J.Tan, EstherWhitworth, Pat W.Bova, Abby R.Anderson, Ian C.Shirinian, MihranTin-u, CaesarO'Rourke, Timothy J.Roberts, Michael S.Francisco, MichaelPierson, A. ScottByeff, Peter D.Kovach, Peter A.Caton, John R.Rarick, Mark UrbanSchimidt, William G.Stopeck, Alison T.Swart, RachelCarrillo Flores, Maria ReginaAlemany, Carlos A.Lozada, BrennelyWeinstein, Paul L.Wang, WeiPorubcin, MichaelEllison, David M.Geils, George F.Rivera, EdgardoCharif, Mahmoud
Issue Date2017
Citation
The Lancet Oncology, 2017, v. 18, n. 12, p. 1688-1700 How to Cite?
AbstractBackground ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. Methods In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1–3c (modified to stage 2–3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1–3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Findings Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1–5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57–0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3–91·8) in the neratinib group and 87·7% (85·7–89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3–4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [<1%] grade 4 with neratinib vs 23 [2%] grade 3 with placebo), vomiting (grade 3: 47 [3%] vs five [<1%]), and nausea (grade 3: 26 [2%] vs two [<1%]). Treatment-emergent serious adverse events occurred in 103 (7%) women in the neratinib group and 85 (6%) women in the placebo group. No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhoea were identified with neratinib compared with placebo. Interpretation At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses—ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast—without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. Funding Wyeth, Pfizer, and Puma Biotechnology.
Persistent Identifierhttp://hdl.handle.net/10722/326475
ISSN
2023 Impact Factor: 41.6
2023 SCImago Journal Rankings: 12.179
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorMartin, Miguel-
dc.contributor.authorHolmes, Frankie A.-
dc.contributor.authorEjlertsen, Bent-
dc.contributor.authorDelaloge, Suzette-
dc.contributor.authorMoy, Beverly-
dc.contributor.authorIwata, Hiroji-
dc.contributor.authorvon Minckwitz, Gunter-
dc.contributor.authorChia, Stephen K.L.-
dc.contributor.authorMansi, Janine-
dc.contributor.authorBarrios, Carlos H.-
dc.contributor.authorGnant, Michael-
dc.contributor.authorTomašević, Zorica-
dc.contributor.authorDenduluri, Neelima-
dc.contributor.authorŠeparović, Robert-
dc.contributor.authorGokmen, Erhan-
dc.contributor.authorBashford, Anna-
dc.contributor.authorRuiz Borrego, Manuel-
dc.contributor.authorKim, Sung Bae-
dc.contributor.authorJakobsen, Erik Hugger-
dc.contributor.authorCiceniene, Audrone-
dc.contributor.authorInoue, Kenichi-
dc.contributor.authorOverkamp, Friedrich-
dc.contributor.authorHeijns, Joan B.-
dc.contributor.authorArmstrong, Anne C.-
dc.contributor.authorLink, John S.-
dc.contributor.authorJoy, Anil Abraham-
dc.contributor.authorBryce, Richard-
dc.contributor.authorWong, Alvin-
dc.contributor.authorMoran, Susan-
dc.contributor.authorYao, Bin-
dc.contributor.authorXu, Feng-
dc.contributor.authorAuerbach, Alan-
dc.contributor.authorBuyse, Marc-
dc.contributor.authorChan, Arlene-
dc.contributor.authorHarvey, Vernon-
dc.contributor.authorTomek, Rudolf-
dc.contributor.authorRobert, Nicholas J.-
dc.contributor.authorGore, Ira-
dc.contributor.authorSmith, John W.-
dc.contributor.authorMasuda, Norikazu-
dc.contributor.authorDi Sean Kendall, S.-
dc.contributor.authorHarker, William Graydon-
dc.contributor.authorPetrakova, Katarina-
dc.contributor.authorGuerrero Zotano, Angel-
dc.contributor.authorSimon, Amparo Ruiz-
dc.contributor.authorKonstantinovic, Zora Neskovic-
dc.contributor.authorIannotti, Nicholas O.-
dc.contributor.authorTassone, Pierfrancesco-
dc.contributor.authorRodriguez, Gladys I.-
dc.contributor.authorJáñez Martinez, Noelia-
dc.contributor.authorCrespo Massieu, Carmen-
dc.contributor.authorSmickoska, Snezana-
dc.contributor.authorSomali, Isil-
dc.contributor.authorYilmaz, Ugur-
dc.contributor.authorAlonso, Mirta Garcia-
dc.contributor.authorRosales, Adolfo Murias-
dc.contributor.authorCold, Soeren-
dc.contributor.authorKnoop, Ann Soegaard-
dc.contributor.authorPatt, Debra-
dc.contributor.authorHellerstedt, Beth A.-
dc.contributor.authorMorales Murillo, Serafin-
dc.contributor.authorMayer, Ingrid A.-
dc.contributor.authorMeans-Powell, Julie Ann-
dc.contributor.authorHui, Rina-
dc.contributor.authorSenecal, Francis M.-
dc.contributor.authorShen, Zhenzhou-
dc.contributor.authorLuczak, Adam Andrzej-
dc.contributor.authorChui, Joanna W.Y.-
dc.contributor.authorTsang, Janice Wing hang-
dc.contributor.authorLang, Istvan-
dc.contributor.authorRai, Yoshiaki-
dc.contributor.authorHozumi, Yasuo-
dc.contributor.authorTen Tije, Albert J.-
dc.contributor.authorBhandari, Manish-
dc.contributor.authorOsborne, Cynthia R.C.-
dc.contributor.authorOhtani, Shoichiro-
dc.contributor.authorHigaki, Kenji-
dc.contributor.authorWatanabe, Kenichi-
dc.contributor.authorTaguchi, Kazunori-
dc.contributor.authorTakahashi, Masato-
dc.contributor.authorFilipovic, Sladjana-
dc.contributor.authorHansen, Vincent L.-
dc.contributor.authorRao, Vijayarama Phooshkooru-
dc.contributor.authorGupta, Manish-
dc.contributor.authorPetrov, Petar-
dc.contributor.authorCoudert, Bruno-
dc.contributor.authorVojnovic, Zeljko-
dc.contributor.authorPolya, Zsofia-
dc.contributor.authorMiyaki, Toshiko-
dc.contributor.authorYamamoto, Naohito-
dc.contributor.authorBrincat, Stephen-
dc.contributor.authorLesniewski-Kmak, Krzysztof-
dc.contributor.authorChmielowska, Ewa-
dc.contributor.authorBirhiray, Ruemu E.-
dc.contributor.authorCitron, Marc L.-
dc.contributor.authorPapish, Steven William-
dc.contributor.authorBerry, William R.-
dc.contributor.authorLangkjer, Sven Tyge-
dc.contributor.authorGarcia Sáenz, José Angel-
dc.contributor.authorArance, Ana Maria-
dc.contributor.authorEfrat, Noa-
dc.contributor.authorSarosiek, Tomasz-
dc.contributor.authorGrzeda, Lukasz-
dc.contributor.authorManalo, Yvonne-
dc.contributor.authorSmith, Julie C.-
dc.contributor.authorVaziri, Irfan-
dc.contributor.authorHealey, Tabitha-
dc.contributor.authorRahim, Yasmin-
dc.contributor.authorLuk, Cynthia-
dc.contributor.authorDingle, Brian-
dc.contributor.authorFranco, Sandra-
dc.contributor.authorSorensen, Peter Grundtvig-
dc.contributor.authorAnand, Anjana-
dc.contributor.authorKhan, Sarah-
dc.contributor.authorFountzilas, George-
dc.contributor.authorAogi, Kenjiro-
dc.contributor.authorShimizu, Satoru-
dc.contributor.authorMikulova, Milada-
dc.contributor.authorSpanik, Stanislav-
dc.contributor.authorSomer, Robert A.-
dc.contributor.authorFlynn, Patrick J.-
dc.contributor.authorCoward, Jermaine-
dc.contributor.authorMainwaring, Paul-
dc.contributor.authorJerusalem, Guy-
dc.contributor.authorSegura-Ojezzar, Carine-
dc.contributor.authorLevy, Christelle-
dc.contributor.authorDelozier, Thierry-
dc.contributor.authorKhayat, David-
dc.contributor.authorColeman, Robert E.-
dc.contributor.authorRolles, Martin J.-
dc.contributor.authorMaisano, Robert-
dc.contributor.authorNardi, Mario-
dc.contributor.authorIto, Yoshinori-
dc.contributor.authorYumuk, Perran Fulden-
dc.contributor.authorBasaran, Gul-
dc.contributor.authorSerdar Turhal, Nazim-
dc.contributor.authorWilkinson, Mary J.-
dc.contributor.authorGreen, Nathan B.-
dc.contributor.authorSidrys, Algis P.-
dc.contributor.authorHallmeyer, Sigrun-
dc.contributor.authorTestori, Douglas J.-
dc.contributor.authorSridhar, Srikala-
dc.contributor.authorChang, Jose-
dc.contributor.authorSun, Qiang-
dc.contributor.authorJara-Sanchez, Carlos-
dc.contributor.authorRubio, Xabier-
dc.contributor.authorGarrido, Maria Lomas-
dc.contributor.authorDe La Haba Rodriguez, Juan Rafael-
dc.contributor.authorPerello Martorell, Antonia-
dc.contributor.authorAvelia Mestre, Antoni-
dc.contributor.authorRifa Ferrer, Julio-
dc.contributor.authordel Barco Berron, Sonia-
dc.contributor.authorNagy, Zsuzsanna-
dc.contributor.authorTanaka, Maki-
dc.contributor.authorIm, Young Hyuck-
dc.contributor.authorCarroll, Robert R.-
dc.contributor.authorDickerson, Laura C.-
dc.contributor.authorMace, Joseph R.-
dc.contributor.authorRivera, Ragene-
dc.contributor.authorKlein, Leonard M.-
dc.contributor.authorRuxer, Robert-
dc.contributor.authorWilks, Sharon T.-
dc.contributor.authorKotasek, Dusan-
dc.contributor.authorPopov, Vasil-
dc.contributor.authorTaskova, Violina-
dc.contributor.authorMarinova-Venkova, Violetka-
dc.contributor.authorTimcheva, Constanta-
dc.contributor.authorDesbiens, Christine-
dc.contributor.authorAyoub, Jean Pierre-
dc.contributor.authorGrenier, Debjani-
dc.contributor.authorMarschner, Norbert-
dc.contributor.authorTesch, Hans-
dc.contributor.authorLueck, Hans Joachim-
dc.contributor.authorJanssen, Jan-
dc.contributor.authorSchwaner, Ingo-
dc.contributor.authorWahlstrom, Stine-
dc.contributor.authorBrix, Eva Harder-
dc.contributor.authorVallentin, Susanne-
dc.contributor.authorKristensen, Dan-
dc.contributor.authorAndreeva, Anna-
dc.contributor.authorGlavicic, Vesna-
dc.contributor.authorCalvo Plaza, Isabel-
dc.contributor.authorAnton Torres, Antonio-
dc.contributor.authorVeyret, Corinne-
dc.contributor.authorBergerat, Jean Pierre-
dc.contributor.authorBourbouloux, Emmanuelle-
dc.contributor.authorElla, Wendy Ann-
dc.contributor.authorAlgurafi, Hafiz-
dc.contributor.authorRobinson, Anne-
dc.contributor.authorKim, Seung Jin-
dc.contributor.authorTaguchi, Tetsuya-
dc.contributor.authorJuozaityte, Elona-
dc.contributor.authorMadretsma, Stanley-
dc.contributor.authorRadema, Sandra-
dc.contributor.authorCzerniawska-Meier, Malgorzata-
dc.contributor.authorRogowski, Wojciech-
dc.contributor.authorWagnerova, Maria-
dc.contributor.authorRichards, Donald A.-
dc.contributor.authorTan-Chiu, Elizabeth-
dc.contributor.authorVasileios, Asskikis-
dc.contributor.authorHenderson, Charles Arthur-
dc.contributor.authorHolden, Viran Roger-
dc.contributor.authorWang, Xiaojia-
dc.contributor.authorTong, Zhongsheng-
dc.contributor.authorYang, Junlan-
dc.contributor.authorGonzalez, Manuel Enrique-
dc.contributor.authorRezai, Mahdi-
dc.contributor.authorHackmann, John-
dc.contributor.authorde Dueñas, Eduardo Martinez-
dc.contributor.authorde las Heras, Begoña Bermejo-
dc.contributor.authorDourthe, Louis Marie-
dc.contributor.authorChocteau-Bouju, Dorothee-
dc.contributor.authorBougnoux, Philippe-
dc.contributor.authorKakolyris, Stylianos-
dc.contributor.authorKalofonos, Haralabos-
dc.contributor.authorPectasidis, Dimitrios-
dc.contributor.authorNg, Ting Ying-
dc.contributor.authorPajkos, Gabor-
dc.contributor.authorSomogyine, Eva Ezer-
dc.contributor.authorTonini, Giuseppe-
dc.contributor.authorGiuffrida, Dario-
dc.contributor.authorTakao, Shintaro-
dc.contributor.authorIshitobi, Makoto-
dc.contributor.authorInaji, Hideo-
dc.contributor.authorTokuda, Yutaka-
dc.contributor.authorWozniak, Katarzyna-
dc.contributor.authorLungulescu, Dan-
dc.contributor.authorLu, Yen Shen-
dc.contributor.authorChang, King Jen-
dc.contributor.authorHill, Julian-
dc.contributor.authorCroot, Christopher Charles-
dc.contributor.authorDekker, Albert-
dc.contributor.authorBelman, Neil D.-
dc.contributor.authorConde, Miguel-
dc.contributor.authorMichaelson, Richard A.-
dc.contributor.authorKemmer, Kathleen-
dc.contributor.authorChui, Stephen-
dc.contributor.authorLuoh, Shiuh Wen-
dc.contributor.authorNahum, Kenneth-
dc.contributor.authorGreenspan, Andrew R.-
dc.contributor.authorNichols, Joni C.-
dc.contributor.authorEncarnacion, Carlos A.-
dc.contributor.authorNiederman, Thomas M.J.-
dc.contributor.authorLee, Theresa-
dc.contributor.authorAlexander, Roland-
dc.contributor.authorGordon, Robert-
dc.contributor.authorTomova, Antoanet-
dc.contributor.authorRauch, Daniel-
dc.contributor.authorPopescu, Razvan Andrei-
dc.contributor.authorRojas, Gustavo Adolfo-
dc.contributor.authorVanasek, Jaroslav-
dc.contributor.authorNeunhoeffer, Tanja-
dc.contributor.authorBarinoff, Jana-
dc.contributor.authorGraffunder, Gerd-
dc.contributor.authorWolfgang, Abenhardt-
dc.contributor.authorBojko, Peter-
dc.contributor.authorHeinrich, Bernhard-
dc.contributor.authorvon der Assen, Albert-
dc.contributor.authorAntonovic, Bogovic Jurij-
dc.contributor.authorAdrian, Lene-
dc.contributor.authorRamos Vazquez, Manuel-
dc.contributor.authorGonzalez Santiago, Santiago-
dc.contributor.authorDieras, Veronique-
dc.contributor.authorBishop, Jill Mercia-
dc.contributor.authorPerren, Timothy John-
dc.contributor.authorVarthalitis, Ioannis-
dc.contributor.authorMavroudis, Dimitris-
dc.contributor.authorGeorgoulias, Vassilis-
dc.contributor.authorChow, Louis W.C.-
dc.contributor.authorYau, Chung Cheung Thomas-
dc.contributor.authorLiang, Raymond Hin Suen-
dc.contributor.authorPikó, Béla-
dc.contributor.authorWéber, Agnes-
dc.contributor.authorKaufman, Bella-
dc.contributor.authorDrumea, Karen-
dc.contributor.authorDe Matteis, Andrea-
dc.contributor.authorNuzzo, Francesco-
dc.contributor.authorCarteni, Giacomo-
dc.contributor.authorTokunaga, Eriko-
dc.contributor.authorIshida, Mayumi-
dc.contributor.authorOhno, Shinji-
dc.contributor.authorSato, Nobuaki-
dc.contributor.authorKuroi, Katsumasa-
dc.contributor.authorNishimura, Reiki-
dc.contributor.authorWatanabe, Junichiro-
dc.contributor.authorChoi, Yoon Ji-
dc.contributor.authorPark, Kyong Hwa-
dc.contributor.authorWojtukiewicz, Marek-
dc.contributor.authorJassem, Jacek-
dc.contributor.authorLoman, Niklas-
dc.contributor.authorAskoy, Sercan-
dc.contributor.authorAltundag, Mustafa Kadri-
dc.contributor.authorSaip, Pinar-
dc.contributor.authorAli, Muhammad Amjad-
dc.contributor.authorWade, James Lloyd-
dc.contributor.authorChien, Amy Jo-
dc.contributor.authorBrandt, Debra-
dc.contributor.authorNovik, Yelena-
dc.contributor.authorJani, Chirag-
dc.contributor.authorRice, Robert L.-
dc.contributor.authorGaffar, Yousuf A.R.-
dc.contributor.authorKeaton, Mark R.-
dc.contributor.authorBajaj, Rajesh-
dc.contributor.authorKimmick, Gretchen-
dc.contributor.authorCampbell, David-
dc.contributor.authorDe Boer, Richard Hendry-
dc.contributor.authorTurnquest, Theodore-
dc.contributor.authorLucas, Sideras-
dc.contributor.authorDube, Pierre-
dc.contributor.authorXu, Binghe-
dc.contributor.authorSchilling, Joerg-
dc.contributor.authorApel, Klaus-
dc.contributor.authorSorensen, Peter Grundtvig-
dc.contributor.authorVestlev, Peter Michael-
dc.contributor.authorJensen, Brita Bjerregaard-
dc.contributor.authorHaahr, Vera-
dc.contributor.authorLescure, Alvaro Rodriguez-
dc.contributor.authorGrana Suarez, Begona-
dc.contributor.authorSaura Manich, Cristina-
dc.contributor.authorJacquin, Jean Philippe-
dc.contributor.authorSamreen, Ahmed-
dc.contributor.authorBoiangiu, Ion-
dc.contributor.authorDank, Magdolna-
dc.contributor.authorFalci, Cristina-
dc.contributor.authorJirillo, Antonio-
dc.contributor.authorCinieri, Saverio-
dc.contributor.authorUeno, Takayuki-
dc.contributor.authorSato, Fumiaki-
dc.contributor.authorYamashiro, Hiroyasu-
dc.contributor.authorSugie, Tomoharu-
dc.contributor.authorLee, Keun Seok-
dc.contributor.authorRo, Jung Sil-
dc.contributor.authorPark, In Hae-
dc.contributor.authorBustam, Anita Zarina-
dc.contributor.authorSuszko-Kazarnowicz, Malgorzata-
dc.contributor.authorPiktel, Artur-
dc.contributor.authorKrzemieniecki, Krzysztof-
dc.contributor.authorIorga, Polizenia Georgeta-
dc.contributor.authorYap, Yoon Sim-
dc.contributor.authorKakalejcik, Marian-
dc.contributor.authorSevinc, Alper-
dc.contributor.authorOzguroglu, Mustafa-
dc.contributor.authorChen, Shin Cheh-
dc.contributor.authorGreenberg, Richard H.-
dc.contributor.authorEisemann, Allan Daniel-
dc.contributor.authorDroder, Robert-
dc.contributor.authorAbbasi, M. Rashid-
dc.contributor.authorVaysburd, Marina-
dc.contributor.authorCaldera, Humberto Jose-
dc.contributor.authorHaley, Barbara Bacsik-
dc.contributor.authorRobin, Erwin-
dc.contributor.authorInhorn, Roger C.-
dc.contributor.authorHufnagel, David-
dc.contributor.authorKenyon, Peter D.-
dc.contributor.authorSpremulli, Ellen-
dc.contributor.authorSilverman, Paula-
dc.contributor.authorJain, Sharad-
dc.contributor.authorWeigand, Robert-
dc.contributor.authorMebis, Jeroen-
dc.contributor.authorKoynova, Tatyana-
dc.contributor.authorLesperance, Bernard-
dc.contributor.authorPrausova, Jana-
dc.contributor.authorKohne, Claus Henning-
dc.contributor.authorSchneeweiss, Andreas-
dc.contributor.authorJackisch, Christian-
dc.contributor.authorFuxius, Stefan-
dc.contributor.authorCubedo Cervera, Ricardo-
dc.contributor.authorUrruticoechea Ribate, Ander-
dc.contributor.authorPernas Simon, Sonia-
dc.contributor.authorValero Gallego, Jose-
dc.contributor.authorArcusa Lanza, Angels-
dc.contributor.authordel Pilar Alvarez, Maria-
dc.contributor.authorFlorian Gerico, Jesus-
dc.contributor.authorCany, Laurent-
dc.contributor.authorStebbing, Justin-
dc.contributor.authorLabudovic, Dejan-
dc.contributor.authorGugic, Damir-
dc.contributor.authorVrbanec, Damir-
dc.contributor.authorRoila, Fausto-
dc.contributor.authorBarni, Sandro-
dc.contributor.authorBidoli, Paolo-
dc.contributor.authorMukai, Hirofumi-
dc.contributor.authorBermudez, Vanessa-
dc.contributor.authorEniu, Alexandru-
dc.contributor.authorMirtsching, Barry C.-
dc.contributor.authorIbrahim, Emad-
dc.contributor.authorTrey, Joan-
dc.contributor.authorHergenroeder, Paul Francis-
dc.contributor.authorMahmood, Aftab-
dc.contributor.authorGonzalez, Anneliese-
dc.contributor.authorKaplan, Edward H.-
dc.contributor.authorBan, Stacy-
dc.contributor.authorPatel, Dhimant-
dc.contributor.authorClowney, Billy-
dc.contributor.authorHoelzer, Karen-
dc.contributor.authorSchwartz, Garry H.-
dc.contributor.authorSalkeni, Mohamed-
dc.contributor.authorAbraham, Jame-
dc.contributor.authorNarula, Sunil-
dc.contributor.authorJabboury, Khaled-
dc.contributor.authorMocharnuk, Robert Scott-
dc.contributor.authorMcDonough, Richard H.-
dc.contributor.authorSikes, David H.-
dc.contributor.authorKawanchi, Ronald H.-
dc.contributor.authorSchlabach, Larry-
dc.contributor.authorMcCachren, Samuel Spence-
dc.contributor.authorCosgriff, Thomas M.-
dc.contributor.authorDreisbach, Luke-
dc.contributor.authorDeMichele, Angela-
dc.contributor.authorPawl, Lawrence-
dc.contributor.authorLucas, Jennifer-
dc.contributor.authorShinn, Lowell C.-
dc.contributor.authorAlkhouri, Nabiel-
dc.contributor.authorMonga, Manish-
dc.contributor.authorLindquist, Deborah L.-
dc.contributor.authorAnderson, Thomas C.-
dc.contributor.authorKhurshid, Humera-
dc.contributor.authorWitherby, Sabrina-
dc.contributor.authorErickson, Nicholette-
dc.contributor.authorTraynor, Ann-
dc.contributor.authorBose, Ron-
dc.contributor.authorPluard, Timothy J.-
dc.contributor.authorJones, Michael C.-
dc.contributor.authorPrakash, Sucharu-
dc.contributor.authorVolterra, Fabio-
dc.contributor.authorCapo, Gerardo-
dc.contributor.authorFlaherty, Lawrence E.-
dc.contributor.authorGartner, Elaina-
dc.contributor.authorBaidas, Said-
dc.contributor.authorOkazaki, Ian-
dc.contributor.authorNguyen, Bichlien-
dc.contributor.authorRakowski, Thomas-
dc.contributor.authorOliff, Ira-
dc.contributor.authorLeach, Joseph W.-
dc.contributor.authorAnderson, Daniel-
dc.contributor.authorKubiak, Kendra-
dc.contributor.authorTsai, Michaela-
dc.contributor.authorVroman, Philippe-
dc.contributor.authorDeleu, Ines-
dc.contributor.authorLybaert, Willem-
dc.contributor.authorBorms, Marleen-
dc.contributor.authorCouture, Felix-
dc.contributor.authorWilson, Jonathan J.-
dc.contributor.authorHunt, Gordon-
dc.contributor.authorHolland, David R.-
dc.contributor.authorMingrone, Walter-
dc.contributor.authorWang, Shusen-
dc.contributor.authorLiu, Donggeng-
dc.contributor.authorJiang, Zefei-
dc.contributor.authorBenesova, Vera-
dc.contributor.authorSmakal, Martin-
dc.contributor.authorGarnolova, Petra-
dc.contributor.authorVesper, Anne Sophie-
dc.contributor.authorNeumann, Monika-
dc.contributor.authorJanni, Wolfgang-
dc.contributor.authorLiedtke, Cornelia-
dc.contributor.authorFischer, Dorothea-
dc.contributor.authorGrischke, Eva Maria-
dc.contributor.authorSeeger, Dietmar-
dc.contributor.authorMoebus, Volker-
dc.contributor.authorPrechtl, Anita-
dc.contributor.authorCarlos Camara Toral, Juan-
dc.contributor.authorSanchez Munoz, Alfonso-
dc.contributor.authorGonzalez Jimenez, Sonia-
dc.contributor.authorCassinello Espinosa, Javier-
dc.contributor.authorCirauqui, Beatriz-
dc.contributor.authorMargeli Vila, Mireia-
dc.contributor.authorBatista Lopez, Norberto-
dc.contributor.authorChacon Lopez-Muniz, Jose Ignacio-
dc.contributor.authorde la Cruz Mora, Miguel Angel-
dc.contributor.authorMailliez, Audrey-
dc.contributor.authorVanlemmens, Laurence-
dc.contributor.authorPouessel, Damien-
dc.contributor.authorEspie, Marc-
dc.contributor.authorConibear, John-
dc.contributor.authorRoylance, Rebecca-
dc.contributor.authorHarnett, Adrian-
dc.contributor.authorGeffen, David-
dc.contributor.authorRuggeri, Enzo Maria-
dc.contributor.authorGamucci, Teresa-
dc.contributor.authorVan Groeningen, Cees J.-
dc.contributor.authorBanas, Renata-
dc.contributor.authorAlkis, Necati-
dc.contributor.authorHou, Ming Feng-
dc.contributor.authorKrie, Amy K.-
dc.contributor.authorVrindavanam, Nandagopal S.-
dc.contributor.authorHoward, Orion M.-
dc.contributor.authorCitrin, Dennis-
dc.contributor.authorMorginstin, Mark S.-
dc.contributor.authorDesai, Ajit-
dc.contributor.authorSanchez, Ines J.-
dc.contributor.authorNixon, David Allen-
dc.contributor.authorBeatty, Patrick G.-
dc.contributor.authorEdmiston, Kathryn-
dc.contributor.authorMcLaughlin, Marilyn-
dc.contributor.authorEneman, Jonathan D.-
dc.contributor.authorLynch, Cynthia A.-
dc.contributor.authorO'Brien, Edward-
dc.contributor.authorCall, Justin A.-
dc.contributor.authorLanier, Keith S.-
dc.contributor.authorConlin, Alison-
dc.contributor.authorBrooks, Donald J.-
dc.contributor.authorMcIntyre, Kristi-
dc.contributor.authorSaltzman, Marc A.-
dc.contributor.authorCastine, Michael J.-
dc.contributor.authorOrtega, Gregory L.-
dc.contributor.authorChoi, Young M.-
dc.contributor.authorReynolds, Craig H.-
dc.contributor.authorBrescia, Frankie Ann-
dc.contributor.authorKramer, Rita-
dc.contributor.authorKohn, Aimee D.-
dc.contributor.authorMicha, John P.-
dc.contributor.authorRhee, Jessica M.-
dc.contributor.authorShah, Satish-
dc.contributor.authorRiseberg, David A.-
dc.contributor.authorPatterson, William Kevin-
dc.contributor.authorSalmon, Jean Paul-
dc.contributor.authorAndre, Chantal-
dc.contributor.authorBols, Alain-
dc.contributor.authorD'hondt, Randal-
dc.contributor.authorLuce, Sylvie-
dc.contributor.authorNouwynck, Claire-
dc.contributor.authorPelgrims, Gino-
dc.contributor.authorRichard, Vincent-
dc.contributor.authorVerschuere, Johan-
dc.contributor.authorGeldhof, Kurt-
dc.contributor.authorCaspar, Clemens-
dc.contributor.authorLuo, Rongcheng-
dc.contributor.authorBednarik, Otakar-
dc.contributor.authorSchwedler, Kathrin-
dc.contributor.authorSchmidt, Marcus-
dc.contributor.authorNeumeister, Romy-
dc.contributor.authorBischoff, Joachim-
dc.contributor.authorRack, Brigitte-
dc.contributor.authorRepp, Roland-
dc.contributor.authorFries, Stefan-
dc.contributor.authorAdrion, Ralf-
dc.contributor.authorSchulz, Volker-
dc.contributor.authorKlare, Peter-
dc.contributor.authorDanei, Mahmoud-
dc.contributor.authorOssenbuhl, Dirk-
dc.contributor.authorKusche, Jakob Manfred-
dc.contributor.authorGriesinger, Frank-
dc.contributor.authorBaena Canada, Jose Manuel-
dc.contributor.authorMartinez del Prado, Purificacion-
dc.contributor.authorMachover, David-
dc.contributor.authorMayeur, Didier-
dc.contributor.authorTrufflandier, Nathalie-
dc.contributor.authorDelecroix, Valerie-
dc.contributor.authorMousseau, Mireille-
dc.contributor.authorMouret-Reynier, Marie Ange-
dc.contributor.authorNabholtz, Jean Marc-
dc.contributor.authorChetiyawardana, Anula D.-
dc.contributor.authorPapandreou, Christos-
dc.contributor.authorHornyak, Lajos-
dc.contributor.authorFaluhelyi, Zsolt-
dc.contributor.authorSimo, Erzsebet-
dc.contributor.authorDi Palma, Mario-
dc.contributor.authorCognetti, Francesco-
dc.contributor.authorGorzegno, Gabriella-
dc.contributor.authorDogliotti, Luigi-
dc.contributor.authorGridelli, Cesare-
dc.contributor.authorFalcone, Alfredo-
dc.contributor.authorSoto Parra, Hector-
dc.contributor.authorBuscarino, Calogero-
dc.contributor.authorIm, Seock Ah-
dc.contributor.authorSanchez Llamas, Benito-
dc.contributor.authorDercksen, Wouter-
dc.contributor.authorErdkamp, Franciscus-
dc.contributor.authorRuit, Jan B.-
dc.contributor.authorBraun, Hans-
dc.contributor.authorPortielje, Joanneke E.A.-
dc.contributor.authorCiltas, Aydin-
dc.contributor.authorBuyukberber, Suleyman-
dc.contributor.authorBenekli, Mustafa-
dc.contributor.authorZahalsky, Andrew J.-
dc.contributor.authorJaslow, Rebecca-
dc.contributor.authorThomas, Gary W.-
dc.contributor.authorMaini, Archana-
dc.contributor.authorWiznitzer, Israel-
dc.contributor.authorKhojasteh, Ali-
dc.contributor.authorFrancisco Gonzalez, Manuel-
dc.contributor.authorKong, Lynn R.-
dc.contributor.authorPadmanabhan, Aruna-
dc.contributor.authorConkright, William A.-
dc.contributor.authorSwain, Sandra M.-
dc.contributor.authorFaig, Douglas E.-
dc.contributor.authorJain, Kirti-
dc.contributor.authorYanagihara, Ronald H.-
dc.contributor.authorOttaviano, Yvonne-
dc.contributor.authorDelmas, Andrew-
dc.contributor.authorSteele, Heather A.-
dc.contributor.authorRainey, Gordon K.-
dc.contributor.authorHarris, Penelope J.-
dc.contributor.authorBurris, Jason K.-
dc.contributor.authorRupard, Erik J.-
dc.contributor.authorTan, Esther-
dc.contributor.authorWhitworth, Pat W.-
dc.contributor.authorBova, Abby R.-
dc.contributor.authorAnderson, Ian C.-
dc.contributor.authorShirinian, Mihran-
dc.contributor.authorTin-u, Caesar-
dc.contributor.authorO'Rourke, Timothy J.-
dc.contributor.authorRoberts, Michael S.-
dc.contributor.authorFrancisco, Michael-
dc.contributor.authorPierson, A. Scott-
dc.contributor.authorByeff, Peter D.-
dc.contributor.authorKovach, Peter A.-
dc.contributor.authorCaton, John R.-
dc.contributor.authorRarick, Mark Urban-
dc.contributor.authorSchimidt, William G.-
dc.contributor.authorStopeck, Alison T.-
dc.contributor.authorSwart, Rachel-
dc.contributor.authorCarrillo Flores, Maria Regina-
dc.contributor.authorAlemany, Carlos A.-
dc.contributor.authorLozada, Brennely-
dc.contributor.authorWeinstein, Paul L.-
dc.contributor.authorWang, Wei-
dc.contributor.authorPorubcin, Michael-
dc.contributor.authorEllison, David M.-
dc.contributor.authorGeils, George F.-
dc.contributor.authorRivera, Edgardo-
dc.contributor.authorCharif, Mahmoud-
dc.date.accessioned2023-03-10T02:19:33Z-
dc.date.available2023-03-10T02:19:33Z-
dc.date.issued2017-
dc.identifier.citationThe Lancet Oncology, 2017, v. 18, n. 12, p. 1688-1700-
dc.identifier.issn1470-2045-
dc.identifier.urihttp://hdl.handle.net/10722/326475-
dc.description.abstractBackground ExteNET showed that 1 year of neratinib, an irreversible pan-HER tyrosine kinase inhibitor, significantly improves 2-year invasive disease-free survival after trastuzumab-based adjuvant therapy in women with HER2-positive breast cancer. We report updated efficacy outcomes from a protocol-defined 5-year follow-up sensitivity analysis and long-term toxicity findings. Methods In this ongoing randomised, double-blind, placebo-controlled, phase 3 trial, eligible women aged 18 years or older (≥20 years in Japan) with stage 1–3c (modified to stage 2–3c in February, 2010) operable breast cancer, who had completed neoadjuvant and adjuvant chemotherapy plus trastuzumab with no evidence of disease recurrence or metastatic disease at study entry. Patients who were eligible patients were randomly assigned (1:1) via permuted blocks stratified according to hormone receptor status (hormone receptor-positive vs hormone receptor-negative), nodal status (0 vs 1–3 vs or ≥4 positive nodes), and trastuzumab adjuvant regimen (given sequentially vs concurrently with chemotherapy), then implemented centrally via an interactive voice and web-response system, to receive 1 year of oral neratinib 240 mg/day or matching placebo. Treatment was given continuously for 1 year, unless disease recurrence or new breast cancer, intolerable adverse events, or consent withdrawal occurred. Patients, investigators, and trial funder were masked to treatment allocation. The predefined endpoint of the 5-year analysis was invasive disease-free survival, analysed by intention to treat. ExteNET is registered with ClinicalTrials.gov, number NCT00878709, and is closed to new participants. Findings Between July 9, 2009, and Oct 24, 2011, 2840 eligible women with early HER2-positive breast cancer were recruited from community-based and academic institutions in 40 countries and randomly assigned to receive neratinib (n=1420) or placebo (n=1420). After a median follow-up of 5·2 years (IQR 2·1–5·3), patients in the neratinib group had significantly fewer invasive disease-free survival events than those in the placebo group (116 vs 163 events; stratified hazard ratio 0·73, 95% CI 0·57–0·92, p=0·0083). The 5-year invasive disease-free survival was 90·2% (95% CI 88·3–91·8) in the neratinib group and 87·7% (85·7–89·4) in the placebo group. Without diarrhoea prophylaxis, the most common grade 3–4 adverse events in the neratinib group, compared with the placebo group, were diarrhoea (561 [40%] grade 3 and one [<1%] grade 4 with neratinib vs 23 [2%] grade 3 with placebo), vomiting (grade 3: 47 [3%] vs five [<1%]), and nausea (grade 3: 26 [2%] vs two [<1%]). Treatment-emergent serious adverse events occurred in 103 (7%) women in the neratinib group and 85 (6%) women in the placebo group. No evidence of increased risk of long-term toxicity or long-term adverse consequences of neratinib-associated diarrhoea were identified with neratinib compared with placebo. Interpretation At the 5-year follow-up, 1 year of extended adjuvant therapy with neratinib, administered after chemotherapy and trastuzumab, significantly reduced the proportion of clinically relevant breast cancer relapses—ie, those that might lead to death, such as distant and locoregional relapses outside the preserved breast—without increasing the risk of long-term toxicity. An analysis of overall survival is planned after 248 events. Funding Wyeth, Pfizer, and Puma Biotechnology.-
dc.languageeng-
dc.relation.ispartofThe Lancet Oncology-
dc.titleNeratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/S1470-2045(17)30717-9-
dc.identifier.pmid29146401-
dc.identifier.scopuseid_2-s2.0-85035115011-
dc.identifier.volume18-
dc.identifier.issue12-
dc.identifier.spage1688-
dc.identifier.epage1700-
dc.identifier.eissn1474-5488-
dc.identifier.isiWOS:000417001900046-

Export via OAI-PMH Interface in XML Formats


OR


Export to Other Non-XML Formats