Enhancing Radioiodine Incorporation into Radioiodine-Refractory Thyroid Cancer with MAPK Inhibition (ERRITI): A Single-Center Prospective Two-Arm Study.
Journal
Clinical cancer research : an official journal of the American Association for Cancer Research
ISSN: 1557-3265
Titre abrégé: Clin Cancer Res
Pays: United States
ID NLM: 9502500
Informations de publication
Date de publication:
03 10 2022
03 10 2022
Historique:
received:
09
02
2022
revised:
04
04
2022
accepted:
17
05
2022
pubmed:
21
5
2022
medline:
5
10
2022
entrez:
20
5
2022
Statut:
ppublish
Résumé
Restoration of iodine incorporation (redifferentiation) by MAPK inhibition was achieved in previously radioiodine-refractory, unresectable thyroid carcinoma (RR-TC). However, results were unsatisfactory in BRAFV600E-mutant (BRAF-MUT) RR-TC. Here we assess safety and efficacy of redifferentiation therapy through genotype-guided MAPK-modulation in patients with BRAF-MUT or wildtype (BRAF-WT) RR-TC. In this prospective single-center, two-arm phase II study, patients received trametinib (BRAF-WT) or trametinib + dabrafenib (BRAF-MUT) for 21 ± 3 days. Redifferentiation was assessed by 123I-scintigraphy. In case of restored radioiodine uptake, 124I-guided 131I therapy was performed. Primary endpoint was the redifferentiation rate. Secondary endpoints were treatment response (thyroglobulin, RECIST 1.1) and safety. Parameters predicting successful redifferentiation were assessed using a receiver operating characteristic analysis and Youden J statistic. Redifferentiation was achieved in 7 of 20 (35%) patients, 2 of 6 (33%) in the BRAF-MUT and 5 of 14 (36%) in the BRAF-WT arm. Patients received a mean (range) activity of 300.0 (273.0-421.6) mCi for 131I therapy. Any thyroglobulin decline was seen in 57% (4/7) of the patients, RECIST 1.1 stable/partial response/progressive disease in 71% (5/7)/14% (1/7)/14% (1/7). Peak standardized uptake value (SUVpeak) < 10 on 2[18F]fluoro-2-deoxy-D-glucose (FDG)-PET was associated with successful redifferentiation (P = 0.01). Transient pyrexia (grade 3) and rash (grade 4) were noted in one patient each. Genotype-guided MAPK inhibition was safe and resulted in successful redifferentiation in about one third of patients in each arm. Subsequent 131I therapy led to a thyroglobulin (Tg) decline in more than half of the treated patients. Low tumor glycolytic rate as assessed by FDG-PET is predictive of redifferentiation success. See related commentary by Cabanillas et al., p. 4164.
Identifiants
pubmed: 35594174
pii: 699089
doi: 10.1158/1078-0432.CCR-22-0437
pmc: PMC9527501
doi:
Substances chimiques
Iodine Radioisotopes
0
Iodine-124
0
Iodine-131
0
Protein Kinase Inhibitors
0
Fluorodeoxyglucose F18
0Z5B2CJX4D
Thyroglobulin
9010-34-8
Proto-Oncogene Proteins B-raf
EC 2.7.11.1
Types de publication
Editorial
Langues
eng
Sous-ensembles de citation
IM
Pagination
4194-4202Commentaires et corrections
Type : CommentIn
Informations de copyright
©2022 The Authors; Published by the American Association for Cancer Research.
Références
J Clin Endocrinol Metab. 2018 Oct 1;103(10):3698-3705
pubmed: 30032208
Oncogene. 2003 Jul 10;22(28):4406-12
pubmed: 12853977
Clin Cancer Res. 2007 Feb 15;13(4):1341-9
pubmed: 17317846
Clin Cancer Res. 2015 Mar 1;21(5):1028-35
pubmed: 25549723
J Clin Endocrinol Metab. 2019 May 1;104(5):1417-1428
pubmed: 30256977
J Nucl Med. 2009 May;50 Suppl 1:122S-50S
pubmed: 19403881
Clin Nucl Med. 2012 Mar;37(3):e47-52
pubmed: 22310270
Endocr Pathol. 2020 Jun;31(2):101-107
pubmed: 32124226
Radiographics. 2016 Jan-Feb;36(1):293-4
pubmed: 26761542
Sci Rep. 2017 Jul 5;7(1):4666
pubmed: 28680105
Arq Bras Endocrinol Metabol. 2010 Dec;54(9):807-12
pubmed: 21340173
Clin Oncol (R Coll Radiol). 2004 Dec;16(8):569-74
pubmed: 15630851
J Nucl Med. 1996 Sep;37(9):1557-62
pubmed: 8790218
J Nucl Med. 2004 Aug;45(8):1366-72
pubmed: 15299063
J Biomed Inform. 2009 Apr;42(2):377-81
pubmed: 18929686
Eur J Cancer. 2009 Jan;45(2):228-47
pubmed: 19097774
J Clin Invest. 2011 Dec;121(12):4700-11
pubmed: 22105174
Clin Endocrinol (Oxf). 2018 Apr;88(4):529-537
pubmed: 29095527
Lancet Diabetes Endocrinol. 2014 May;2(5):356-8
pubmed: 24795243
J Natl Cancer Inst. 2003 Apr 16;95(8):625-7
pubmed: 12697856
J Thyroid Res. 2012;2012:618985
pubmed: 22530159
Thyroid. 2016 May;26(5):672-82
pubmed: 26971368
Endocr Relat Cancer. 2006 Mar;13(1):257-69
pubmed: 16601293
Q J Nucl Med Mol Imaging. 2011 Feb;55(1):21-43
pubmed: 21386783
Lancet Oncol. 2016 Sep;17(9):1272-82
pubmed: 27460442
Curr Opin Cell Biol. 2009 Apr;21(2):296-303
pubmed: 19231149
Ann Oncol. 2017 Jul 01;28(7):1631-1639
pubmed: 28475671
Cancer Res. 2003 Apr 1;63(7):1454-7
pubmed: 12670889
Oncogene. 2003 Jul 17;22(29):4578-80
pubmed: 12881714
Eur Thyroid J. 2019 Oct;8(5):227-245
pubmed: 31768334
Thyroid. 2008 Jul;18(7):697-704
pubmed: 18630997
Nuklearmedizin. 2012;51(4):111-5
pubmed: 22532159
Clin Cancer Res. 2000 Apr;6(4):1279-87
pubmed: 10778952
J Clin Invest. 2016 Nov 1;126(11):4119-4124
pubmed: 27669459
Clin Cancer Res. 2010 Feb 1;16(3):978-85
pubmed: 20103666
J Clin Endocrinol Metab. 2006 Aug;91(8):2892-9
pubmed: 16684830
J Nucl Med. 2014 Nov;55(11):1759-65
pubmed: 25332440
J Clin Endocrinol Metab. 2007 Jul;92(7):2840-3
pubmed: 17488796
Thyroid. 2019 Nov;29(11):1634-1645
pubmed: 31637953
N Engl J Med. 2013 Feb 14;368(7):623-32
pubmed: 23406027
Thyroid. 2016 Jan;26(1):1-133
pubmed: 26462967
Endocr J. 2009;56(1):105-12
pubmed: 18854619
Endocr Relat Cancer. 2020 May;27(5):R113-R132
pubmed: 32191916
J Clin Endocrinol Metab. 2017 Jun 1;102(6):1898-1907
pubmed: 28323937
Thyroid. 2019 Mar;29(3):311-321
pubmed: 30747050
Oncotarget. 2017 Jun 27;8(26):42252-42261
pubmed: 28178685
Endocr Relat Cancer. 2011 Jan 13;18(1):159-69
pubmed: 21118976
World J Surg. 1998 Jun;22(6):569-74
pubmed: 9597930
N Engl J Med. 2012 Nov;367(18):1694-703
pubmed: 23020132
Thyroid. 2015 Jan;25(1):71-7
pubmed: 25285888
Cancer Res. 2005 Mar 15;65(6):2465-73
pubmed: 15781663