Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate: an analysis of the NETTER-1 study.
(Clinical Trial, Phase III;Journal Article)
PURPOSE: 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.
Strosberg, J; Kunz, PL; Hendifar, A; Yao, J; Bushnell, D; Kulke, MH; Baum, RP; Caplin, M; Ruszniewski, P; Delpassand, E; Hobday, T; Verslype, C; Benson, A; Srirajaskanthan, R; Pavel, M; Mora, J; Berlin, J; Grande, E; Reed, N; Seregni, E; Paganelli, G; Severi, S; Morse, M; Metz, DC; Ansquer, C; Courbon, F; Al-Nahhas, A; Baudin, E; Giammarile, F; Taïeb, D; Mittra, E; Wolin, E; O'Dorisio, TM; Lebtahi, R; Deroose, CM; Grana, CM; Bodei, L; Öberg, K; Polack, BD; He, B; Mariani, MF; Gericke, G; Santoro, P; Erion, JL; Ravasi, L; Krenning, E; NETTER-1 study group,
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