Synapse - Phase I trial of well-differentiated neuroendocrine tumors (NETs) with radiolabeled somatostatin antagonist (177)Lu-satoreotide tetraxetan

Phase I trial of well-differentiated neuroendocrine tumors (NETs) with radiolabeled somatostatin antagonist (177)Lu-satoreotide tetraxetan Journal Article

Authors:	Reidy-Lagunes, D.; Pandit-Taskar, N.; O'Donoghue, J. A.; Krebs, S.; Staton, K. D.; Lyashchenko, S. K.; Lewis, J. S.; Raj, N.; Gönen, M.; Lohrmann, C.; Bodei, L.; Weber, W. A.
Article Title:	Phase I trial of well-differentiated neuroendocrine tumors (NETs) with radiolabeled somatostatin antagonist (177)Lu-satoreotide tetraxetan
Abstract:	Purpose: Radiolabeled somatostatin receptor 2 (SSTR2) antagonists have shown higher tumor uptake and tumor-to-organ ratios than somatostatin agonists in preclinical models of neuroendocrine tumors (NETs). We performed a phase I study to evaluate the safety and efficacy of SSTR2 antagonist Lu-177-satoreotide tetraxetan. Patients and Methods: Twenty patients with advanced SSTR2-positive NETs were treated with Lu-177-satoreotide tetraxetan. Patients first underwent a dosimetry study with Lu-177-satoreotide tetraxetan to determine the therapeutic activity that could be safely administered. This activity was split into two equal cycles to be delivered 3 months apart. The maximum activity was 7.4 GBq per cycle. Results: Of 20 patients with NETs (one lung, seven small bowel, nine pancreatic, one gastric, one rectal, one kidney; mean prior treatments: three), six received one cycle of Lu-177-satoreotide tetraxetan and 14 received two cycles. Hematologic toxicity after cycle 1 was mild-moderate and reversed before cycle 2. However, grade 4 hematologic toxicity occurred in four of seven (57%) patients after cycle 2 of Lu-177-satoreotide tetraxetan. The study was suspended, and the protocol modified to limit the cumulative absorbed bone marrow dose to 1 Gy and to reduce prescribed activity for cycle 2 by 50%. The best overall response rate was 45% [5% complete response (1/20), 40% partial response (8/20)]; with 40% stable disease (8/20) and 15% progression of disease (3/20). Median progression-free survival (PFS) was 21.0 months (95% CI, 13.6-NR). Conclusions: In this trial of heavily treated NETs, preliminary data are promising for the use of Lu-177-satoreotide tetraxetan. Additional studies are ongoing to determine optimal therapeutic dose/schedule.
Keywords:	dosimetry; toxicity; sensitivity; bone-marrow; analog; agonist; receptor radionuclide therapy; prrt; lu-177-dotatate
Journal Title:	Clinical Cancer Research
Volume:	25
Issue:	23
ISSN:	1078-0432
Publisher:	American Association for Cancer Research
Date Published:	2019-12-01
Start Page:	6939
End Page:	6947
Language:	English
ACCESSION:	WOS:000500953700010
DOI:	10.1158/1078-0432.Ccr-19-1026
PROVIDER:	wos
PUBMED:	31439583
PMCID:	PMC8382090
Notes:	Article -- Source: Wos