Please use this identifier to cite or link to this item: https://observatorio.fm.usp.br/handle/OPI/33668
Title: Afatinib vs Placebo as Adjuvant Therapy After Chemoradiotherapy in Squamous Cell Carcinoma of the Head and Neck: A Randomized Clinical Trial
Authors: BURTNESS, BarbaraHADDAD, RobertDINIS, JoseTRIGO, JoseYOKOTA, TomoyaVIANA, Luciano de SouzaROMANOV, IlyaVERMORKEN, JanBOURHIS, JeanTAHARA, MakotoSEGALLA, Jose Getulio MartinsPSYRRI, AmandaVASILEVSKAYA, IrinaNANGIA, Chaitali SinghCHAVES-CONDE, ManuelKIYOTA, NaomiHOMMA, AkihiroHOLECKOVA, PetraCAMPO, Josep Maria DelASARAWALA, NiravNICOLAU, Ulisses RibaldoRAUCH, DanielEVEN, CarolineWANG, BushiGIBSON, NeilEHRNROOTH, EvaHARRINGTON, KevinCOHEN, Ezra E. W.GIGLIO, Raul EduardoBLAJMAN, Cesar RaulFREUE, Jose MarioPILNIK, Norma GracielaPALAZZO, Felipe SalvadorMCGRATH, MargaretFUREDER, ThorstenKORNEK, GabrielaPICHLER, AngelikaBAUERNHOFER, ThomasTINCHON, ChristophGREIL, RichardBURIAN, MartinKIENZER, HeinzSPECENIER, PolSAUTOIS, BrieucDEBRUYNE, PhilipGRAAS, Marie-PascaleMAES, AnneliesLONCHAY, ChristopheDAISNE, Jean-FrancoisFONTAINE, ChristelCASTRO JUNIOR, GilbertoOLIVEIRA, Frias dePEREIRA, Rodrigo PerezMARCHI, Pedro Rafael Martins DeVIANA, Luciano de SouzaSEGALLA, Jose Getulio MartinsNICOLAU, Ulisses RibaldoLAZARETTI, Nicolas SilvaKULKARNI, SwatiALAM, YasminHO, CherylSHENOUDA, GeorgeSOULIERES, DenisSULTANEM, KhalilSINGH, SimronMELLA, Pablo GonzalezCAMPOS, Jose Antonio SolisHOLECKOVA, PetraPRAUSOVA, JanaOBERMANNOVA, RadkaFRIBORG, JeppeSPECHT, LenaELSAID, Amr AbdelazizMINN, HeikkiMARTIN, LaurentROLLAND, FredericCERUSE, PhilippeCALAIS, GillesEVEN, CarolineGUIGAY, JoeFERTE, CharlesPEYRADE, FredericDUFFAUD, FlorenceCHAMPEAUX-ORANGE, EliseCOUTTE, AlexandreCLATOT, FlorianFOURNEL, PierreMOAL, Laurence Bozec LeDIETZ, AndreasGRUENWALD, ViktorGAULER, ThomasGUNTINAS-LICHIUS, OrlandoHILDEBRANDT, GuidoKUHNT, ThomasSCHMIDT, Horst-JuergenHENKE, MichaelRUECKERT, AnjaBRUGGER, WolframROTTER, NicoleMAHLBERG, RolfKARAVASILIS, VasiliosFOUNTZILAS, GeorgiosPSYRRI, DiamantoLANG, IstvanBOER, AndrasKOCSIS, JuditPAJKOS, GaborTAMAS, LaszloANAND, A. L.SHARMA, AjaySharmaVOONA, MuraliPANDY, Ananda SelvakumarKUMAR, KirushnaNATHAN, Raj Kumar PoovnaSRINIVASAN, VenkatesanZADE, BhooshanJAIN, MinishSRINIVASA, B. J.NAIK, RadheshyamMOHANTY, B. K.ASARAWALA, NiravCHARAS, TomerBILLAN, SalemPOPOVTZER, AronLICITRA, LisaFERRARI, DarisFAO, PaoloMERLANO, MarcoROCCA, Maria CossuHOMMA, AkihiroFUJII, HirofumiTAHARA, MakotoMINAMI, SyujiroFUJII, MasatoYOKOTA, TomoyaKADOWAKI, ShigenoriMURO, KeiKIYOTA, NaomiOKAMI, KenjiYAGI, ToshinariYOSHINO, KunitoshiMATSUMOTO, KojiTAKAHASHI, ShunjiMATSUURA, KazutoAVITIA, Miguel Angel AlvarezRIESTRA, Hector Jorge GonzalezMEERTEN, E. vanBUTER, J.GELDERBLOM, A. J.KAWECKI, AndrzejGOLUSINSKI, WojciechDINIS, JoseDINIS, RuiRIBEIRO, LeonorSILVA, ReginaMANSINHO, HelderSELEZNEVA, IrinaBIAKHOV, MikhailGALIULIN, RinatIZMAILOV, AdelROMANOV, IlyaVLADIMIROV, VladimirVINOGRADOV, ValeryMUFAZALOV, FagimVASILEVSKAYA, IrinaBASTE, NeusCAMPO, Josep Ma delNIN, Ricard MesiaPOUSA, Antonio LopezCASTRO, Juan Jose Grau deREIG, OscarVERA, RuthTRIGO, JoseManuelIGLESIAS, LaraTRUFERO, Javier MartinezVAZQUEZ, SergioRUBIO, BelenALES, Jose EnriqueVILLAR, EstherRUBIO, JordiESCOBAR, YolandaSORIA, AinaraCHAVES, MauelJOHANSSON, Gun WickartFRIESLAND, SigneTELL, RogerNYMAN, JanROTHSCHILD, SachaZIPPELIUS, AlfredRAUCH, DanielUSLUOGLU, NurguelGOGUNSKA, InnaZABOLOTNIY, DmytroVINNYK, YuriyBURIAN, OleksandrHARRINGTON, KevinSYKES, AndrewPEEL, DavidLESTER, JamesROBINSON, MartinSRINIVASAN, DevrajFRAGKANDREA-NIXON, IoannaJUNOR, ElizabethGOLLINS, SimonEVANS, MereridNEWBOLD, KateHWANG, DavidSCHIPANI, StefanoRIZWANULLAH, MohammedATIQ, OmarARNAOUTAKIS, KonstantinosBAUMAN, JessicaBURTNESS, BarbaraMEHRA, RaneeKANG, HyunseokCHUNG, ChristineDAVIS, ThomasHADDAD, RobertJIMENO, AntonioKERESZTES, RogerNANGIA, ChaitaliIGNATIUS, Sai-HongSU, Yungpo BernardOVERTON, Lindsay CarolGARRISON, Mitchell A.JEONG, WoondongWEHBE, AhmadARGIRIS, AthanassiosCHIANG, AnneMORGENSZTERN, DanielHAIGENTZ JR., MissakMARTINCIC, DankoPOROSNICU, Mercedes
Citation: JAMA ONCOLOGY, v.5, n.8, p.1170-1180, 2019
Abstract: ImportanceLocoregionally advanced head and neck squamous cell cancer (HNSCC) is treated curatively; however, risk of recurrence remains high among some patients. The ERBB family blocker afatinib has shown efficacy in recurrent or metastatic HNSCC. ObjectiveTo assess whether afatinib therapy after definitive chemoradiotherapy (CRT) improves disease-free survival (DFS) in patients with HNSCC. Design, Setting, and ParticipantsThis multicenter, phase 3, double-blind randomized clinical trial (LUX-Head & Neck 2) studied 617 patients from November 2, 2011, to July 4, 2016. Patients who had complete response after CRT, comprising radiotherapy with cisplatin or carboplatin, with or without resection of residual disease, for locoregionally advanced high- or intermediate-risk HNSCC of the oral cavity, hypopharynx, larynx, or oropharynx were included in the study. Data analysis was of the intention-to-treat population. InterventionsPatients were randomized (2:1) to treatment with afatinib (40 mg/d) or placebo, stratified by nodal status (N0-2a or N2b-3) and Eastern Cooperative Oncology Group performance status (0 or 1). Treatment continued for 18 months or until disease recurrence, unacceptable adverse events, or patient withdrawal. Main Outcomes and MeasuresThe primary end point was DFS, defined as time from the date of randomization to the date of tumor recurrence or secondary primary tumor or death from any cause. Secondary end points were DFS at 2 years, overall survival (defined as time from the date of randomization to death), and health-related quality of life. ResultsA total of 617 patients were studied (mean [SD] age, 58 [8.4] years; 528 male [85.6%]). Recruitment was stopped after a preplanned interim futility analysis on July 4, 2016, on recommendation from an independent data monitoring committee. Treatment was discontinued. Median DFS was 43.4 months (95% CI, 37.4 months to not estimable) in the afatinib group and not estimable (95% CI, 40.1 months to not estimable) in the placebo group (hazard ratio, 1.13; 95% CI, 0.81-1.57; stratified log-rank test P=.48). The most common grade 3 and 4 drug-related adverse effects were acneiform rash (61 [14.8%] of 411 patients in the afatinib group vs 1 [0.5%] of 206 patients in the placebo group), stomatitis (55 [13.4%] in the afatinib group vs 1 [0.5%] in the placebo group), and diarrhea (32 [7.8%] in the afatinib group vs 1 [0.5%] in the placebo group). Conclusions and RelevanceThis study's findings indicate that treatment with afatinib after CRT did not improve DFS and was associated with more adverse events than placebo in patients with primary, unresected, clinically high- to intermediate-risk HNSCC. The use of adjuvant afatinib after CRT is not recommended. Trial RegistrationClinicalTrials.gov identifier: NCT01345669
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Artigos e Materiais de Revistas Científicas - FM/MDR
Departamento de Radiologia - FM/MDR

Artigos e Materiais de Revistas Científicas - HC/ICESP
Instituto do Câncer do Estado de São Paulo - HC/ICESP

Artigos e Materiais de Revistas Científicas - LIM/24
LIM/24 - Laboratório de Oncologia Experimental


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