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

Jonathan Strosberg, Pamela L Kunz, Andrew Hendifar, James Yao, David Bushnell, Matthew H Kulke, Richard P Baum, Martyn Caplin, Philippe Ruszniewski, Ebrahim Delpassand, Timothy Hobday, Chris Verslype, Al Benson, Rajaventhan Srirajaskanthan, Marianne Pavel, Jaume Mora, Jordan Berlin, Enrique Grande, Nicholas Reed, Ettore SeregniGiovanni Paganelli, Stefano Severi, Michael Morse, David C Metz, Catherine Ansquer, Frédéric Courbon, Adil Al-Nahhas, Eric Baudin, Francesco Giammarile, David Taïeb, Erik Mittra, Edward Wolin, Thomas M O'Dorisio, Rachida Lebtahi, Christophe M Deroose, Chiara M Grana, Lisa Bodei, Kjell Öberg, Berna Degirmenci Polack, Beilei He, Maurizio F Mariani, Germo Gericke, Paola Santoro, Jack L Erion, Laura Ravasi, Eric Krenning

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)2372-2382
Number of pages11
JournalEuropean Journal of Nuclear Medicine and Molecular Imaging
Volume47
Issue number10
DOIs
Publication statusPublished - Sep 2020

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