1. 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
- Author
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Strosberg, Jonathan, Kunz, Pamela L, Hendifar, Andrew, Yao, James, Bushnell, David, Kulke, Matthew H, Baum, Richard P, Caplin, Martyn, Ruszniewski, Philippe, Delpassand, Ebrahim, Hobday, Timothy, Verslype, Chris, Benson, Al, Srirajaskanthan, Rajaventhan, Pavel, Marianne, Mora, Jaume, Berlin, Jordan, Grande, Enrique, Reed, Nicholas, Seregni, Ettore, Paganelli, Giovanni, Severi, Stefano, Morse, Michael, Metz, David C, Ansquer, Catherine, Courbon, Frédéric, Al-Nahhas, Adil, Baudin, Eric, Giammarile, Francesco, Taïeb, David, Mittra, Erik, Wolin, Edward, O’Dorisio, Thomas M, Lebtahi, Rachida, Deroose, Christophe M, Grana, Chiara M, Bodei, Lisa, Öberg, Kjell, Polack, Berna Degirmenci, He, Beilei, Mariani, Maurizio F, Gericke, Germo, Santoro, Paola, Erion, Jack L, Ravasi, Laura, and Krenning, Eric
- Subjects
Biomedical and Clinical Sciences ,Oncology and Carcinogenesis ,Digestive Diseases ,Clinical Research ,Clinical Trials and Supportive Activities ,Cancer ,Alkaline Phosphatase ,Humans ,Liver Neoplasms ,Neuroendocrine Tumors ,Octreotide ,Organometallic Compounds ,Treatment Outcome ,NETTER-1 study group ,177Lu-Dotatate ,Liver tumour burden ,NETTER-1 ,Neuroendocrine tumour ,Other Physical Sciences ,Clinical Sciences ,Nuclear Medicine & Medical Imaging ,Clinical sciences - Abstract
PurposeTo assess the impact of baseline liver tumour burden, alkaline phosphatase (ALP) elevation, and target lesion size on treatment outcomes with 177Lu-Dotatate.MethodsIn 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.ResultsSignificantly prolonged median PFS occurred with 177Lu-Dotatate versus octreotide LAR 60 mg in patients with low ( 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.Conclusions177Lu-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.
- Published
- 2020