Westin, Shannon N.Moore, KathleenChon, Hye SookThomes Pepin, JessicaSundborg, MichaelShai, AyeletNishio, ShinGold, Michael A.Wang, KeKirtbaya, DmitriyKreynina, JulyaLim, Sheow LeiBourhaba, MaryamCarney, MichaelGe, LouGordinier, MaryGuy, MichaelHartenbach, EllenHaygood, ChistenJordan, ScottJoseph de Padua, Charles AndreeProvencher, DianeSafina, SufiaKilgore, LarryAktas, BahriyeGupta, SudeepKim, YoungDevinder, PaulDebruyne, PhilipGen-Hai, ZhuLucci, JosephMccollum, MichaelNovak, ZoltanLopez, Carolina OrtizPapadimitriou, ChristosYu, ZhangMchale, MichaelMcintyre, KristiMessing, MarkKrabisch, PetraMiller, EirwenMoroney, JohnEgger, EvaPoka, RobertGoyal, LovenishSipocz, IstvanGuiling, LiOnstad, MichaelaZhiqing, LiangSalinas, ErinDenys, HanneloreSharma, SudarshanSobol, UrszulaSoliman, PamelaEdraki, BabakStarks, DavidBrasiuniene, BiruteJonuskiene, GodaTeplinsky, EleonoraTakehara, KazuhiroBruchim, IlanContreras Mejia, FernandoTillmanns, ToddNaik, RadheshyamMuller, AndreasRosengarten, OraWarshal, DavidWoliver, ThomasForget, FredericLazaretti, NicolasDonnelly, ConorRosario, Paula Michelle delLiu, XiaochunInciura, ArturasHernandez, Angel LuisNieuwenhuysen, Els vanSafra, TamarMartins Vieira, CarolinaPirmagomedov, AlbertMattar, AndreMakarova, YuliaNeves Palmeiro, DanielaPatil, TusharPimentel Oppermann-Kussler, ChristinaRubini Liedke, Pedro EmanuelRyu, Sang YoungLópez Hernández, JesúsYamagami, WataruNunes, Joao SoaresCabrera Luviano, Jesús ElvisTiscoski, Katsuki ArimaCovens, AllanGuerke, Lara deHong, ZhengGhatage, PrafullGilbert, LucyLau, SusieSong, Yong JungHamanishi, JunzoOrlova, RashidaLisyanskaya, AllaSomashekhar, S.P.Oza, Amit M.Domínguez Andrade, AdrianaHongwu, WenJi-Hong, LiuWimberger, PaulineJing, WangKe, WangImai, YuichiRoncolato, FeliciaKui, JiangLi, LiDepasquale, StephenLi, WangChen, Lee-MaySuso, Juan PabloGerson-Cwilich, RaquelMin, HaoSaevets, ValeriaFernández Pérez, IsauraQi, ZhouSoh, Lay TinQinglei, GaoSihai, LiaoSongling, ZhangFountzilas, GeorgeZorr, AndreasWeidong, ZhaoWu, XiaohuaGarza, Joseph de laChambers, SetsukoHernández Hernández, CarlosWuliang, WangAlarcón Company, JesúsPacheco, Carlos JavierKovel, SvetlanaRamos Guette, Pedro LuisRendon Pereira, JaimeRivera Diaz, JulianSkopin, PavelSánchez Villegas, TomasPennington, KathrynKarageorgopoulou, SofiaOrtiz, TaylorFox, JennyBarretina, PilarPsyrri, AmandaDisilvestro, PaulZagour, FloraiLoen Chan, Karen KarHo, Wing MingLeibovici, AncaLiu, Ji-HongTillmanns, Todd D.Csoszi, TiborLandherr, LaszloOzair, SobiaEstévez García, PurificaciónPapai, ZsuzsannaKado, NobuhiroMileshkin, LindaKamiura, ShojiRom, JoachimTyulyandina, AlexandraVettus, ElenKato, HienoriKondo, EijiFrentzas, SophiaRose, PeterKudaka, WataruPfaendler, KristaMatsumoto, TakashiMori, MasahikoOkamoto, AikouMartinez Lira, José LuísYunokawa, MayuSekine, MasayukiSumi, ToshiyukiGanessan, KichendasseMeniawy, TarekGao, BoFleming, EvelynTakano, HirokuniPriebe, AnnaNavarrete Aleman, Jaime EstebanSu Mien, Lynette NgoReyes Contreras, JessicaRosas Camargo, VanessaBednarek, WieslawaBlank, Stephanie V.Kubiatowski, TomaszNishikawa, TadaakiCongzhu, LiPotemski, PiotrSperfeld, AntjeCuypere, Eveline dePustilnik, TerriSikorska, MagdalenaRichardson, GaryChang, Suk-JoonHonhon, BrigitteHong, Sook HeeKang, SokbomShao Peng, David TanGálvez, FernandoKim, Byoung-GieKim, Jan-WeonKim, Yong ManTouhami, OmarResnick, KimberlyLee, Jung-YunJoosens, EricTorregroza Otero, Marco AntonioKlasa-Mazurkiewicz, DagmaraMelo, Andreia Cristina deGarcía, YolandaGil Martín, MartaBaurain, Jean FrancoisMartínez, JerónimoRedondo Sánchez, AndrésYin, RutieHong, ShiCosta Miranda, Vanessa daAnderson, CharlesDanbo, WangBerman, TaraBlank, StephanieBradley, WilliamGold, MichaelBurke, JamesGrisan, KarinCappuccini, FabioYing, ChengGuedes, Joao DanielSehouli, Jalid2024-07-012024-07-012024-01-201527-7755https://hdl.handle.net/2445/214044PURPOSE Immunotherapy and chemotherapy combinations have shown activity in endometrial cancer, with greater benefit in mismatch repair (MMR)-deficient (dMMR) than MMR-proficient (pMMR) disease. Adding a poly(ADP-ribose) polymerase inhibitor may improve outcomes, especially in pMMR disease. METHODS This phase III, global, double-blind, placebo-controlled trial randomly assigned eligible patients with newly diagnosed advanced or recurrent endometrial cancer 1:1:1 to: carboplatin/paclitaxel plus durvalumab placebo followed by placebo maintenance (control arm); carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib placebo (durvalumab arm); or carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab plus olaparib (durvalumab + olaparib arm). The primary end points were progression-free survival (PFS) in the durvalumab arm versus control and the durvalumab + olaparib arm versus control. RESULTS Seven hundred eighteen patients were randomly assigned. In the intention-to-treat population, statistically significant PFS benefit was observed in the durvalumab (hazard ratio [HR], 0.71 [95% CI, 0.57 to 0.89]; P = .003) and durvalumab + olaparib arms (HR, 0.55 [95% CI, 0.43 to 0.69]; P < .0001) versus control. Prespecified, exploratory subgroup analyses showed PFS benefit in dMMR (HR [durvalumab v control], 0.42 [95% CI, 0.22 to 0.80]; HR [durvalumab + olaparib v control], 0.41 [95% CI, 0.21 to 0.75]) and pMMR subgroups (HR [durvalumab v control], 0.77 [95% CI, 0.60 to 0.97]; HR [durvalumab + olaparib v control] 0.57; [95% CI, 0.44 to 0.73]); and in PD-L1-positive subgroups (HR [durvalumab v control], 0.63 [95% CI, 0.48 to 0.83]; HR [durvalumab + olaparib v control], 0.42 [95% CI, 0.31 to 0.57]). Interim overall survival results (maturity approximately 28%) were supportive of the primary outcomes (durvalumab v control: HR, 0.77 [95% CI, 0.56 to 1.07]; P = .120; durvalumab + olaparib v control: HR, 0.59 [95% CI, 0.42 to 0.83]; P = .003). The safety profiles of the experimental arms were generally consistent with individual agents. CONCLUSION Carboplatin/paclitaxel plus durvalumab followed by maintenance durvalumab with or without olaparib demonstrated a statistically significant and clinically meaningful PFS benefit in patients with advanced or recurrent endometrial cancer.20 p.application/pdfengcc by-nc-nd (c) Westin, Shannon N. et al, 2024http://creativecommons.org/licenses/by-nc-nd/3.0/es/Anticossos monoclonalsCàncer d'endometriMonoclonal antibodiesEndometrial cancerinfo:eu-repo/semantics/article2024-06-28info:eu-repo/semantics/openAccess37864337