Treatment Response and Clinical Outcomes of Well-Differentiated High-Grade Neuroendocrine Tumors to Lutetium-177-DOTATATE.
177Lu-DOTATATE
High-grade neuroendocrine tumors
Neuroendocrine tumors
Peptide receptor-radiolabeled therapy
Journal
Neuroendocrinology
ISSN: 1423-0194
Titre abrégé: Neuroendocrinology
Pays: Switzerland
ID NLM: 0035665
Informations de publication
Date de publication:
2022
2022
Historique:
received:
04
02
2022
accepted:
16
05
2022
pubmed:
25
5
2022
medline:
19
11
2022
entrez:
24
5
2022
Statut:
ppublish
Résumé
Lutetium-177 (177Lu)-DOTATATE received FDA approval in 2018 to treat somatostatin receptor-positive gastroenteropancreatic neuroendocrine tumors (NETs). Little data are available on response and outcomes for well-differentiated (WD) high-grade (HG) NETs treated with 177Lu-DOTATATE. Patients with WD HG NETs treated with 177Lu-DOTATATE at MSK from 2018 to 2020 were identified. Demographics, response (RECIST 1.1), and progression-free survival (PFS) were determined. Next-generation sequencing (NGS) was performed in the archival tumor. Nineteen patients, all with progressive, heavily treated disease, were identified. Sites of tumor origin were: pancreas (74%), small bowel (11%), rectum (11%), and lung (5%); median Ki-67 was 32% (range 22-56). Thirteen patients (68%) completed all four 177Lu-DOTATATE cycles. Best response (N = 18 evaluable) was: 5/18 (28%) partial response, 8/18 (44%) stable disease, and 5/18 (28%) disease progression. Median PFS was 13.1 months (95% CI: 8.7-20.9). Most common treatment-related toxicities were thrombocytopenia (9 patients, 47%; G3/4, 1 patient, 5%), anemia (7 patients, 37%; G3/4, 2 patients, 11%), leukopenia (6 patients, 32%; G3/4, 0 patients), and liver function test elevation (4 patients, 21%; G3/4, 0 patients). NGS results were available from 13/19 tumors (68%). The most observed alterations were in MEN1 (6/13, 46%) and DAXX (4/13, 31%). No RB1 alterations identified. We observed a meaningful disease control rate of 72% during treatment of WD HG NETs with 177Lu-DOTATATE. In this heavily pre-treated population, more than half of patients received all four treatment cycles with toxicities largely bone marrow-related. As would be expected in WD NETs, the vast majority had alterations in chromatin remodeling genes and no RB1 alterations.
Identifiants
pubmed: 35609558
pii: 000525216
doi: 10.1159/000525216
pmc: PMC9671816
mid: NIHMS1814378
doi:
Substances chimiques
Lutetium-177
BRH40Y9V1Q
copper dotatate CU-64
0
Octreotide
RWM8CCW8GP
Lutetium
5H0DOZ21UJ
Radioisotopes
0
Organometallic Compounds
0
Radiopharmaceuticals
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1177-1186Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Informations de copyright
© 2022 S. Karger AG, Basel.
Références
Eur J Endocrinol. 2004 Jul;151(1):15-27
pubmed: 15248818
Ann Oncol. 2013 Jan;24(1):152-60
pubmed: 22967994
Mol Imaging Biol. 2003 Jan-Feb;5(1):42-8
pubmed: 14499161
Eur J Nucl Med Mol Imaging. 2018 Feb;45(2):262-277
pubmed: 28894897
J Clin Oncol. 2011 Aug 1;29(22):3085-96
pubmed: 21383288
Clin Cancer Res. 2016 Feb 15;22(4):1011-7
pubmed: 26482044
Endocr Relat Cancer. 2021 Nov 11;29(1):1-14
pubmed: 34647903
Cancer Discov. 2012 Jan;2(1):82-93
pubmed: 22585170
Cancers (Basel). 2021 Apr 10;13(8):
pubmed: 33920195
J Nucl Med. 2007 Apr;48(4):508-18
pubmed: 17401086
Am J Surg Pathol. 2015 May;39(5):683-90
pubmed: 25723112
J Mol Diagn. 2015 May;17(3):251-64
pubmed: 25801821
Nature. 2017 Mar 2;543(7643):65-71
pubmed: 28199314
J Nucl Med. 2010 Jun;51(6):875-82
pubmed: 20484441
Science. 2011 Mar 4;331(6021):1199-203
pubmed: 21252315
Eur J Nucl Med Mol Imaging. 2004 Aug;31(8):1097-104
pubmed: 15029459
JCO Precis Oncol. 2018;2018:
pubmed: 30687805
Biomed Pharmacother. 2008 Dec;62(10):667-71
pubmed: 18358680
Nat Biotechnol. 2009 Feb;27(2):182-9
pubmed: 19182786
Surgery. 2016 Mar;159(3):862-71
pubmed: 26602841
N Engl J Med. 2017 Jan 12;376(2):125-135
pubmed: 28076709
J Nucl Med. 2019 Mar;60(3):377-385
pubmed: 30115686
Endocrinol Metab Clin North Am. 2018 Sep;47(3):463-470
pubmed: 30098710
Gastroenterology. 2010 Sep;139(3):742-53, 753.e1
pubmed: 20637207
Endocr Relat Cancer. 2019 Feb 1;26(2):227-239
pubmed: 30540557
Eur J Nucl Med Mol Imaging. 2007 Oct;34(10):1617-26
pubmed: 17520251
Eur J Nucl Med Mol Imaging. 2003 May;30(5):781-93
pubmed: 12707737
Eur J Nucl Med. 2001 Dec;28(12):1751-7
pubmed: 11734911
Pancreas. 2017 Mar;46(3):296-301
pubmed: 27759713