Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with (177)Lu-Dotatate: An analysis of the NETTER-1 study Journal Article


Authors: Strosberg, J.; Kunz, P. L.; Hendifar, A.; Yao, J.; Bushnell, D.; Kulke, M. H.; Baum, R. P.; 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, D. C.; Ansquer, C.; Courbon, F.; Al-Nahhas, A.; Baudin, E.; Giammarile, F.; Taïeb, D.; Mittra, E.; Wolin, E.; O’Dorisio, T. M.; Lebtahi, R.; Deroose, C. M.; Grana, C. M.; Bodei, L.; Öberg, K.; Polack, B. D.; He, B.; Mariani, M. F.; Gericke, G.; Santoro, P.; Erion, J. L.; Ravasi, L.; Krenning, E.; on behalf of the NETTER-1 study group
Article Title: Impact of liver tumour burden, alkaline phosphatase elevation, and target lesion size on treatment outcomes with (177)Lu-Dotatate: An analysis of the NETTER-1 study
Abstract: 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 © 2020, The Author(s).
Keywords: octreotide; neuroendocrine tumour; 177lu-dotatate; liver tumour burden; netter-1
Journal Title: European Journal of Nuclear Medicine and Molecular Imaging
Volume: 47
Issue: 10
ISSN: 1619-7070
Publisher: Springer  
Date Published: 2020-09-01
Start Page: 2372
End Page: 2382
Language: English
DOI: 10.1007/s00259-020-04709-x
PUBMED: 32123969
PROVIDER: scopus
PMCID: PMC7396396
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Lisa   Bodei
    140 Bodei