Strosberg, JonathanKunz, Pamela L.Hendifar, AndrewYao, JamesBushnell, DavidKulke, Matthew H.Baum, Richard P.Caplin, MartynRuszniewski, PhilippeDelpassand, EbrahimHobday, TimothyVerslype, ChrisBenson, AlSrirajaskanthan, RajaventhanPavel, MarianneMora Salvador, JaumeBerlin, JordanGrande, EnriqueReed, NicholasSeregni, EttorePaganelli, GiovanniSeveri, StefanoMorse, MichaelMetz, David C.Ansquer, CatherineCourbin, FrédéricAl-Nahhas, AdilBaudin, EricGiammarile, FrancescoTaïeb, DavidMittra, ErikWolin, EdwardO’Dorisio, Thomas M.Lebtahi, RachidaDeroose, Christophe M.Grana, Chiara M.Bodei, LisaÖberg, KjellPolack, Berna DegirmenciHe, BeileiMariani, Maurizio F.Gericke, GermoSantoro, PaolaErion, Jack L.Ravasi, LauraKrenning, EricNetter-1 Study GroupEuclid Collaboration2021-02-262021-02-262020-03-02https://hdl.handle.net/2445/174399Purpose: To assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate. Methods: In the phase 3 NETTER-1 trial, patients with advanced, progressive midgut neuroendocrine tumours (NET) were randomised to 177Lu-Dotatate (every 8 weeks, four cycles) plus octreotide long-acting release (LAR) or to octreotide LAR 60 mg. Primary endpoint was progression-free survival (PFS). Analyses of PFS by baseline factors, including liver tumour burden, ALP elevation, and target lesion size, were performed using Kaplan-Meier estimates; hazard ratios (HRs) with corresponding 95% CIs were estimated using Cox regression. Results: Significantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low (< 25%), moderate (25-50%), and high (> 50%) liver tumour burden (HR 0.187, 0.216, 0.145), and normal or elevated ALP (HR 0.153, 0.177), and in the presence or absence of a large target lesion (diameter > 30 mm; HR, 0.213, 0.063). Within the 177Lu-Dotatate arm, no significant difference in PFS was observed amongst patients with low/moderate/high liver tumour burden (P = 0.7225) or with normal/elevated baseline ALP (P = 0.3532), but absence of a large target lesion was associated with improved PFS (P = 0.0222). Grade 3 and 4 liver function abnormalities were rare and did not appear to be associated with high baseline liver tumour burden. Conclusions: 177Lu-Dotatate demonstrated significant prolongation in PFS versus high-dose octreotide LAR in patients with advanced, progressive midgut NET, regardless of baseline liver tumour burden, elevated ALP, or the presence of a large target lesion. Clinicaltrials.gov : NCT01578239, EudraCT: 2011-005049-11.11 p.application/pdfengcc by (c) Strosberg et al., 2020http://creativecommons.org/licenses/by/3.0/es/TumorsCàncer de fetgeTumorsLiver cancerinfo:eu-repo/semantics/article2021-02-16info:eu-repo/semantics/openAccess32123969