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For placebo or observational studies in this condition, please visit this page.
Note: these are regimens tested in histology-specific populations, please see the main thyroid cancer page for other regimens.

11 regimens on this page 14 variants on this page

Guidelines

Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.

ATA

2015: Guidelines on the management of thyroid nodules and differentiated thyroid cancer PubMed

ESMO

2019: Filetti et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2012: Pacini et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Pacini et al. Differentiated thyroid cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Pacini et al. Differentiated thyroid cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed

NCCN

NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Thyroid Carcinoma.

Adjuvant therapy

Radioiodine ablation

Regimen variant #1, 1.1 GBq

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schlumberger et al. 2012 (ESTIMABL1)	2007-2010	Phase 3 (E-de-esc)	I-131; 3.7 GBq	Equivalent rate of ablation (primary endpoint)
Mallick et al. 2012 (HiLo)	2007-2010	Phase 3 (E-de-esc)	I-131; 3.7 GBq	Non-inferior rate of ablation (primary endpoint)
Leboulleux et al. 2022 (ESTIMABL2)	2013-2017	Phase 3 (C)	Observation	Non-inferior composite endpoint

Preceding treatment

Thyroidectomy

Radiotherapy

Iodine-131 1.1 GBq

One course

Regimen variant #2, 3.7 GBq

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schlumberger et al. 2012 (ESTIMABL1)	2007-2010	Phase 3 (C)	I-131; 1.1 GBq	Equivalent outcome
Mallick et al. 2012 (HiLo)	2007-2010	Phase 3 (C)	I-131; 1.1 GBq	Non-inferior rate of ablation
Ho et al. 2022 (ASTRA)	2013-2016	Phase 3 (C)	RAI & Selumetinib	Did not meet primary endpoint of CR rate at 18 months

Preceding treatment

Thyroidectomy

Radiotherapy

Iodine-131 3.7 GBq

One course

Regimen variant #3, variable

Study	Dates of enrollment	Evidence
Maxon et al. 1983	1974-12 to 1982-07	Non-randomized

Note: "The amount of 131I administered was arbitrarily determined by whoever was treating the patient"; included here for historic reference only.

Preceding treatment

Thyroidectomy

Radiotherapy

Iodine-131

References

Case report: Seidlin SM, Marinelli LD, Oshry E. Radioactive iodine therapy; effect on functioning metastases of adenocarcinoma of the thyroid. J Am Med Assoc. 1946 Dec 7;132(14):838-47. link to original article PubMed
Maxon HR, Thomas SR, Hertzberg VS, Kereiakes JG, Chen IW, Sperling MI, Saenger EL. Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med. 1983 Oct 20;309(16):937-41. link to original article PubMed
SYTJ001T/2000: Mäenpää HO, Heikkonen J, Vaalavirta L, Tenhunen M, Joensuu H. Low vs. high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a randomized study. PLoS One. 2008 Apr 2;3(4):e1885. link to original article link to PMC article PubMed NCT00115895
1. Update: Ahtiainen V, Vaalavirta L, Tenhunen M, Joensuu H, Mäenpää H. Randomised comparison of 1.1 GBq and 3.7 GBq radioiodine to ablate the thyroid in the treatment of low-risk thyroid cancer: a 13-year follow-up. Acta Oncol. 2020 Sep;59(9):1064-1071. Epub 2020 Jun 30. link to original article PubMed
ESTIMABL1: Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, Bardet S, Leenhardt L, Bastie D, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Bonichon F, Dejax C, Toubert ME, Leboulleux S, Ricard M, Benhamou E; Tumeurs de la Thyroïde Refractaires Network for the Essai Stimulation Ablation Equivalence Trial. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012 May 3;366(18):1663-73. link to original article PubMed NCT00435851
1. Update: Schlumberger M, Leboulleux S, Catargi B, Deandreis D, Zerdoud S, Bardet S, Rusu D, Godbert Y, Buffet C, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Toubert ME, Kelly A, Benhamou E, Borget I. Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial. Lancet Diabetes Endocrinol. 2018 Aug;6(8):618-626. Epub 2018 May 26. link to original article PubMed
HiLo: Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012 May 3;366(18):1674-85. link to original article contains dosing details in abstract PubMed NCT00415233
ASTRA: Ho AL, Dedecjus M, Wirth LJ, Tuttle RM, Inabnet WB 3rd, Tennvall J, Vaisman F, Bastholt L, Gianoukakis AG, Rodien P, Paschke R, Elisei R, Viola D, So K, Carroll D, Hovey T, Thakre B, Fagin JA; ASTRA investigator group. Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA). J Clin Oncol. 2022 Jun 10;40(17):1870-1878. Epub 2022 Feb 22. link to original article contains dosing details in abstract link to PMC article PubMed NCT01843062
ESTIMABL2: Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L, Dygai I, Vera P, Rusu D, Schneegans O, Benisvy D, Klein M, Roux J, Eberle MC, Bastie D, Nascimento C, Giraudet AL, Le Moullec N, Bardet S, Drui D, Roudaut N, Godbert Y, Morel O, Drutel A, Lamartina L, Schvartz C, Velayoudom FL, Schlumberger MJ, Leenhardt L, Borget I. Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer. N Engl J Med. 2022 Mar 10;386(10):923-932. link to original article contains dosing details in abstract PubMed NCT01837745

Radioiodine & Selumetinib

Regimen

Study	Dates of enrollment	Evidence
Ho et al. 2013 (MSK 09-048)	2010-2011	Non-randomized

Radiotherapy

Iodine-131 (dose not specified)

Targeted therapy

Selumetinib (Koselugo) 75 mg PO twice per day on days 1 to 28

4-week course

References

MSK 09-048: Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Domínguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013 Feb 14;368(7):623-32. link to original article link to PMC article PubMed NCT00970359

Advanced or metastatic disease, radioactive iodine-refractory

Apatinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lin et al. 2022 (REALITY)	2017-2020	Phase 3 (E-esc)	Placebo	Seems to have superior OS (secondary endpoint) Median OS: NYR vs 29.9 mo (HR 0.42, 95% CI 0.18-0.97)

Targeted therapy

Apatinib (Aitan) 500 mg PO once per day on days 1 to 28

28-day cycles

References

REALITY: Lin Y, Qin S, Li Z, Yang H, Fu W, Li S, Chen W, Gao Z, Miao W, Xu H, Zhang Q, Zhao X, Bao J, Li L, Ren Y, Lin C, Jing S, Ma Q, Liang J, Chen G, Zhang H, Zhang Y, Zhou X, Sang Y, Hou Z. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer: The REALITY Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):242-250. link to original article link to PMC article contains dosing details in manuscript PubMed NCT03048877

Cabozantinib monotherapy

Regimen variant #1, pediatric dosing

FDA-recommended dose

Note: this is the FDA-recommended dose in pediatric patients who are 12 years of age or older with BSA less than 1.2 m².

Targeted therapy

Cabozantinib (Cometriq) 40 mg PO once per day

Continued indefinitely

Regimen variant #2

FDA-recommended dose

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Brose et al. 2021 (COSMIC-311)	2019-02-27 to 2020-08-18	Phase 3 (E-RT-esc)	Placebo	Superior PFS (co-primary endpoint) Median PFS: NYR vs 1.9 mo (HR 0.22, 96% CI 0.13-0.36)

Note: this is the FDA-recommended dose for adult patients.

Targeted therapy

Cabozantinib (Cometriq) 60 mg PO once per day on days 1 to 28

28-day cycles

References

COSMIC-311: Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Hernando J, Faoro L, Banerjee K, Oliver JW, Keam B, Capdevila J. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1126-1138. Epub 2021 Jul 5. link to original article contains dosing details in manuscript PubMed NCT03690388

Donafenib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Lin et al. 2023 (ZGDD3)	2018-08-29 to 2021-02-28	Phase 3 (E-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 12.9 vs 6.4 mo (HR 0.39, 95% CI 0.25-0.61)

Targeted therapy

Donafenib (Zepsun) 300 mg PO twice per day on days 1 to 28

28-day cycles

References

ZGDD3: Lin Y, Qin S, Yang H, Shi F, Yang A, Han X, Liu B, Li Z, Ji Q, Tang L, Deng Z, Ding Y, Fu W, Xie X, Li L, He X, Lv Z, Ma Q, Shen Z, Guo Z, Chen Z, Cui Y, Tan J, Gao Z, Jing S, Lu K, Luo X, Zhang Y, Fang Y, Li Z, Cheng Y, Lei S, Luan S, Chen G, Wang G, Wu L, Liu L. Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer. Clin Cancer Res. 2023 Aug 1;29(15):2791-2799. link to original article contains dosing details in manuscript PubMed NCT03602495

Lenvatinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Schlumberger et al. 2015 (SELECT)	2011-08-05 to 2012-10-04	Phase 3 (E-RT-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 18.3 vs 3.6 mo (HR 0.21, 99% CI 0.14-0.31)
Zheng et al. 2021 (E7080-C086-308)	2017-NR	Phase 3 (E-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 23.9 vs 3.7 mo (HR 0.16, 95% CI 0.10-0.26)

Targeted therapy

Lenvatinib (Lenvima) 24 mg PO once per day on days 1 to 28

28-day cycles

Dose and schedule modifications

Per the package insert, patients with eGFR of less than 30 mL/min/1.73m² by Cockroft-Gault or Child-Pugh C severe hepatic impairment should receive 14 mg PO once per day.

References

SELECT: Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. link to original article contains dosing details in abstract PubMed NCT01321554
E7080-C086-308: Zheng X, Xu Z, Ji Q, Ge M, Shi F, Qin J, Wang F, Chen G, Zhang Y, Huang R, Tan J, Huang T, Li S, Lv Z, Lin Y, Guo Z, Kubota T, Suzuki T, Ikezawa H, Gao M. A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer. Clin Cancer Res. 2021 Oct 15;27(20):5502-5509. Epub 2021 Jul 29. link to original article contains dosing details in abstract link to PMC article PubMed NCT02966093

Pazopanib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Bible et al. 2010 (MC057H)	2008-2009	Phase 2

Targeted therapy

Pazopanib (Votrient) 800 mg PO once per day on days 1 to 28

28-day cycles

References

MC057H: Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM, Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C; Endocrine Malignancies Disease Oriented Group; Mayo Clinic Cancer Center; Mayo Phase 2 Consortium. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010 Oct;11(10):962-72. Epub 2010 Sep 17. link to original article contains dosing details in abstract link to PMC article PubMed NCT00625846

Sorafenib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Brose et al. 2014 (DECISION)	2009-2011	Phase 3 (E-RT-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 10.8 vs 5.8 mo (HR 0.59, 95% CI 0.45-0.76)

Targeted therapy

Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 28

28-day cycles

References

DECISION: Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Peña C, Molnár I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. Epub 2014 Apr 24. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00984282

Sunitinib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Efficacy
Carr et al. 2010	2007-2009	Phase 2	ORR: 31% (95% CI: 16-47)

Targeted therapy

Sunitinib (Sutent) 37.5 mg PO once per day on days 1 to 42

42-day cycles

References

Carr LL, Mankoff DA, Goulart BH, Eaton KD, Capell PT, Kell EM, Bauman JE, Martins RG. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res. 2010 Nov 1;16(21):5260-8. Epub 2010 Sep 16. link to original article contains dosing details in manuscript link to PMC article PubMed

Vandetanib monotherapy

Regimen

Study	Dates of enrollment	Evidence	Comparator	Comparative Efficacy
Leboulleux et al. 2012 (D4200C00079)	2007-2008	Randomized Phase 2 (E-esc)	Placebo	Superior PFS (primary endpoint) Median PFS: 11.1 vs 5.9 mo (HR 0.63, 60% CI 0.54-0.74)

Targeted therapy

Vandetanib (Caprelsa) 300 mg PO once per day

Continued indefinitely

References

D4200C00079: Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gómez JM, Bonichon F, Leenhardt L, Soufflet C, Licour M, Schlumberger MJ. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012 Sep;13(9):897-905. Epub 2012 Aug 14. link to original article contains dosing details in abstract PubMed NCT00537095

Advanced or metastatic disease, all lines of therapy

Axitinib monotherapy

Regimen

Study	Dates of enrollment	Evidence
Locati et al. 2014 (A4061027)	2006-2008	Phase 2

Targeted therapy

Axitinib (Inlyta) 5 mg PO twice per day

Continued indefinitely

References

A4061027: Locati LD, Licitra L, Agate L, Ou SH, Boucher A, Jarzab B, Qin S, Kane MA, Wirth LJ, Chen C, Kim S, Ingrosso A, Pithavala YK, Bycott P, Cohen EE. Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer. 2014 Sep 1;120(17):2694-703. Epub 2014 May 20. link to original article contains dosing details in manuscript PubMed NCT00389441

@@ Line 3: / Line 3: @@
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 </div>
-{{#lst:Section editor transclusions|endo}}
+{{#lst:Editorial board transclusions|endo}}
+''For placebo or observational studies in this condition, please visit [[Thyroid cancer, differentiated - null regimens|this page]].''<br>
 Note: these are regimens tested in histology-specific populations, please see the '''[[Thyroid cancer|main thyroid cancer page]]''' for other regimens.
 {| class="wikitable" style="float:right; margin-right: 5px;"
@@ Line 12: / Line 13: @@
 {{TOC limit|limit=3}}
 =Guidelines=
+'''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.'''
 ==[https://www.thyroid.org/ ATA]==
-*'''2015:''' Guidelines on the management of thyroid nodules and differentiated thyroid cancer [https://pubmed.ncbi.nlm.nih.gov/28114862 PubMed]
+*'''2015:''' [https://doi.org/10.1089/thy.2016.0628 Guidelines on the management of thyroid nodules and differentiated thyroid cancer] [https://pubmed.ncbi.nlm.nih.gov/28114862/ PubMed]
-==[http://www.esmo.org/ ESMO]==
-*'''2019:''' Filetti et al. [https://doi.org/10.1093/annonc/mdz400 Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+==[https://www.esmo.org/ ESMO]==
-===Older===
+*'''2019:''' Filetti et al. [https://doi.org/10.1093/annonc/mdz400 Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://www.ncbi.nlm.nih.gov/pubmed/31549998 PubMed]
-*'''2012:''' Pacini et al. [http://annonc.oxfordjournals.org/content/23/suppl_7/vii110.full.pdf+html Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/22997443 PubMed]
+**'''2012:''' Pacini et al. [https://doi.org/10.1093/annonc/mds230 Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/22997443/ PubMed]
-==[https://www.nccn.org/ NCCN]==
+**'''2009:''' Pacini et al. [https://doi.org/10.1093/annonc/mdp156 Differentiated thyroid cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454437/ PubMed]
-*[https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf NCCN Guidelines - Thyroid Carcinoma]
+**'''2008:''' Pacini et al. [https://doi.org/10.1093/annonc/mdn115 Differentiated thyroid cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456786/ PubMed]
-=All lines of therapy=
-==Cabozantinib monotherapy {{#subobject:1dgac6|Regimen=1}}==
+==NCCN==
-<div class="toccolours" style="background-color:#eeeeee">
+*''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1470 NCCN Guidelines - Thyroid Carcinoma].''
-===Regimen variant #1, pediatric dosing {{#subobject:1gacnd|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
+=Adjuvant therapy=
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
-''Note: this is the FDA-recommended dose in pediatric patients who are 12 years of age or older with BSA less than 1.2 m<sup>2</sup>.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Cabozantinib (Cometriq)]] 40 mg PO once per day
-'''Continued indefinitely'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:1hzndd|Variant=1}}===
-{| class="wikitable" style="color:white; background-color:#404040"
-|<small>'''FDA-recommended dose'''</small>
-|-
-|}
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/s1470-2045(21)00332-6 Brose et al. 2021 (COSMIC-311)]
-|2019-2020
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: NYR vs 1.9 mo<br>(HR 0.22, 96% CI 0.13-0.36)
-|-
-|}
-''Note: this is the FDA-recommended dose for adult patients.''
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Cabozantinib (Cometriq)]] 60 mg PO once per day
-'''Continued indefinitely'''
-</div></div>
-===References===
-# '''COSMIC-311:''' Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Hernando J, Faoro L, Banerjee K, Oliver JW, Keam B, Capdevila J. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1126-1138. Epub 2021 Jul 5. [https://doi.org/10.1016/s1470-2045(21)00332-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34237250/ PubMed] NCT03690388
-==Lenvatinib monotherapy {{#subobject:PYR1|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:PYV1|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1056/NEJMoa1406470 Schlumberger et al. 2015 (SELECT)]
-{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-135-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
-|-
-|}
-|2011-2012
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 18.3 vs 3.6 mo<br>(HR 0.21, 99% CI 0.14-0.31)
-|-
-|[https://doi.org/10.1158/1078-0432.ccr-21-0761 Zheng et al. 2021 (E7080-C086-308)]
-|2017-NR
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 23.9 vs 3.7 mo<br>(HR 0.16, 95% CI 0.10-0.26)
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Lenvatinib (Lenvima)]] 24 mg PO once per day
-**Per the package insert, patients with eGFR of less than 30 mL/min/1.73m<sup>2</sup> by Cockroft-Gault or Child-Pugh C severe hepatic impairment should receive 14 mg PO once per day
-'''28-day cycles'''
-</div></div>
-===References===
-<!-- # '''Abstract:''' Martin Schlumberger, Makoto Tahara, Lori J. Wirth, Bruce Robinson, Marcia S. Brose, Rossella Elisei, Corina E. Dutcus, Begoña de las Heras, Junming Zhu, Mouhammed Amir Habra, Kate Newbold, Manisha H. Shah, Ana O. Hoff, Andrew G Gianoukakis, Naomi Kiyota, Matthew Hiram Taylor, Sung-Bae Kim, Monika K Krzyzanowska, Steven I. Sherman. A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). 2014 ASCO Annual Meeting abstract LBA6008. [http://meetinglibrary.asco.org/content/132694-144 link to abstract] -->
-# '''SELECT:''' Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. [https://doi.org/10.1056/NEJMoa1406470 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25671254 PubMed] NCT01321554
-#'''E7080-C086-308:''' Zheng X, Xu Z, Ji Q, Ge M, Shi F, Qin J, Wang F, Chen G, Zhang Y, Huang R, Tan J, Huang T, Li S, Lv Z, Lin Y, Guo Z, Kubota T, Suzuki T, Ikezawa H, Gao M. A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer. Clin Cancer Res. 2021 Oct 15;27(20):5502-5509. Epub 2021 Jul 29. [https://doi.org/10.1158/1078-0432.ccr-21-0761 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34326132/ PubMed] NCT02966093
-==Pazopanib monotherapy {{#subobject:4ee26c|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8faae3|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107731/ Bible et al. 2010 (MC057H)]
-|2008-2009
-| style="background-color:#91cf61" |Phase 2
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
-*[[Pazopanib (Votrient)]] 800 mg PO once per day
-'''28-day cycles'''
-</div></div>
-===References===
-# '''MC057H:''' Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM,  Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C; Endocrine Malignancies Disease Oriented Group; Mayo Clinic Cancer Center; Mayo Phase 2 Consortium. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010 Oct;11(10):962-72. Epub 2010 Sep 17. [https://doi.org/10.1016/s1470-2045(10)70203-5 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107731/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20851682 PubMed] NCT00625846
-==Placebo==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|-
-|[https://doi.org/10.1016/S1470-2045(12)70335-2 Leboulleux et al. 2012 (D4200C00079)]
-|2007-2008
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Vandetanib_monotherapy|Vandetanib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366116/ Brose et al. 2014 (DECISION)]
-|2009-2011
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Sorafenib_monotherapy|Sorafenib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|[https://doi.org/10.1056/NEJMoa1406470 Schlumberger et al. 2015 (SELECT)]
-|2011-2012
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Lenvatinib_monotherapy|Lenvatinib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|[https://doi.org/10.1016/s1470-2045(21)00332-6 Brose et al. 2021 (COSMIC-311)]
-|2019-2020
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cabozantinib_monotherapy|Cabozantinib]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|}
-''No active antineoplastic treatment.''
-</div></div>
-===References===
-# '''D4200C00079:''' Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gómez JM, Bonichon F, Leenhardt L, Soufflet C, Licour M, Schlumberger MJ. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012 Sep;13(9):897-905. Epub 2012 Aug 14. [https://doi.org/10.1016/S1470-2045(12)70335-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22898678 PubMed] NCT00537095
-# '''DECISION:''' Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Peña C, Molnár I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. Epub 2014 Apr 24. [https://doi.org/10.1016/s0140-6736(14)60421-9 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24768112 PubMed] NCT00984282
-<!-- # '''Abstract:''' Martin Schlumberger, Makoto Tahara, Lori J. Wirth, Bruce Robinson, Marcia S. Brose, Rossella Elisei, Corina E. Dutcus, Begoña de las Heras, Junming Zhu, Mouhammed Amir Habra, Kate Newbold, Manisha H. Shah, Ana O. Hoff, Andrew G Gianoukakis, Naomi Kiyota, Matthew Hiram Taylor, Sung-Bae Kim, Monika K Krzyzanowska, Steven I. Sherman. A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). 2014 ASCO Annual Meeting abstract LBA6008. [http://meetinglibrary.asco.org/content/132694-144 link to abstract] -->
-# '''SELECT:''' Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. [https://doi.org/10.1056/NEJMoa1406470 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25671254 PubMed] NCT01321554
-# '''COSMIC-311:''' Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Hernando J, Faoro L, Banerjee K, Oliver JW, Keam B, Capdevila J. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1126-1138. Epub 2021 Jul 5. [https://doi.org/10.1016/s1470-2045(21)00332-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34237250/ PubMed] NCT03690388
 ==Radioiodine ablation {{#subobject:29fcfa|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 167: / Line 33: @@
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 176: / Line 42: @@
 | style="background-color:#1a9851" |Phase 3 (E-de-esc)
 |[[#Radioiodine_ablation|I-131]]; 3.7 GBq
-| style="background-color:#eeee01" |Equivalent rate of ablation
+| style="background-color:#eeee01" |Equivalent rate of ablation (primary endpoint)
 |-
 |[https://doi.org/10.1056/NEJMoa1109589 Mallick et al. 2012 (HiLo)]
@@ Line 182: / Line 48: @@
 | style="background-color:#1a9851" |Phase 3 (E-de-esc)
 |[[#Radioiodine_ablation|I-131]]; 3.7 GBq
-| style="background-color:#eeee01" |Non-inferior rate of ablation
+| style="background-color:#eeee01" |Non-inferior rate of ablation (primary endpoint)
 |-
 |[https://doi.org/10.1056/nejmoa2111953 Leboulleux et al. 2022 (ESTIMABL2)]
 |2013-2017
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Observation_88|Observation]]
+|[[Thyroid cancer, differentiated - null regimens#Observation|Observation]]
 | style="background-color:#eeee01" |Non-inferior composite endpoint
 |-
@@ Line 204: / Line 70: @@
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
@@ Line 221: / Line 87: @@
 | style="background-color:#eeee01" |Non-inferior rate of ablation
 |-
-|[https://doi.org/10.1200/jco.21.00714 Ho et al. 2022 (ASTRA)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851689/ Ho et al. 2022 (ASTRA)]
 |2013-2016
 | style="background-color:#1a9851" |Phase 3 (C)
@@ Line 241: / Line 107: @@
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
 |[https://doi.org/10.1056/NEJM198310203091601 Maxon et al. 1983]
-|NR in abstract
+|1974-12 to 1982-07
 | style="background-color:#91cf61" |Non-randomized
 |-
@@ Line 258: / Line 124: @@
 *[[Iodine-131]]
 </div></div>
 ===References===
-# '''Case report:''' Seidlin SM, Marinelli LD, Oshry E. Radioactive iodine therapy; effect on functioning metastases of adenocarcinoma of the thyroid. J Am Med Assoc. 1946 Dec 7;132(14):838-47. [https://jamanetwork.com/journals/jama/article-abstract/290151 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20274882 PubMed]
+# '''Case report:''' Seidlin SM, Marinelli LD, Oshry E. Radioactive iodine therapy; effect on functioning metastases of adenocarcinoma of the thyroid. J Am Med Assoc. 1946 Dec 7;132(14):838-47. [https://jamanetwork.com/journals/jama/article-abstract/290151 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20274882/ PubMed]
-# Maxon HR, Thomas SR, Hertzberg VS, Kereiakes JG, Chen IW, Sperling MI, Saenger EL. Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med. 1983 Oct 20;309(16):937-41. [https://doi.org/10.1056/NEJM198310203091601 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6621620 PubMed]
+# Maxon HR, Thomas SR, Hertzberg VS, Kereiakes JG, Chen IW, Sperling MI, Saenger EL. Relation between effective radiation dose and outcome of radioiodine therapy for thyroid cancer. N Engl J Med. 1983 Oct 20;309(16):937-41. [https://doi.org/10.1056/NEJM198310203091601 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6621620/ PubMed]
-#'''SYTJ001T/2000:''' Mäenpää HO, Heikkonen J, Vaalavirta L, Tenhunen M, Joensuu H. Low vs. high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a randomized study. PLoS One. 2008 Apr 2;3(4):e1885. [https://doi.org/10.1371/journal.pone.0001885 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2270902/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18382668/ PubMed] NCT00115895
+#'''SYTJ001T/2000:''' Mäenpää HO, Heikkonen J, Vaalavirta L, Tenhunen M, Joensuu H. Low vs. high radioiodine activity to ablate the thyroid after thyroidectomy for cancer: a randomized study. PLoS One. 2008 Apr 2;3(4):e1885. [https://doi.org/10.1371/journal.pone.0001885 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2270902/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/18382668/ PubMed] [https://clinicaltrials.gov/study/NCT00115895 NCT00115895]
 ## '''Update:''' Ahtiainen V, Vaalavirta L, Tenhunen M, Joensuu H, Mäenpää H. Randomised comparison of 1.1 GBq and 3.7 GBq radioiodine to ablate the thyroid in the treatment of low-risk thyroid cancer: a 13-year follow-up. Acta Oncol. 2020 Sep;59(9):1064-1071. Epub 2020 Jun 30. [https://doi.org/10.1080/0284186x.2020.1785003 link to original article] [https://pubmed.ncbi.nlm.nih.gov/32603613/ PubMed]
-# '''ESTIMABL1:''' Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, Bardet S, Leenhardt L, Bastie D, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Bonichon F, Dejax C, Toubert ME, Leboulleux S, Ricard M, Benhamou E; Tumeurs de la Thyroïde Refractaires Network for the Essai Stimulation Ablation Equivalence Trial. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012 May 3;366(18):1663-73. [https://doi.org/10.1056/NEJMoa1108586 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22551127 PubMed] NCT00435851
+# '''ESTIMABL1:''' Schlumberger M, Catargi B, Borget I, Deandreis D, Zerdoud S, Bridji B, Bardet S, Leenhardt L, Bastie D, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Bonichon F, Dejax C, Toubert ME, Leboulleux S, Ricard M, Benhamou E; Tumeurs de la Thyroïde Refractaires Network for the Essai Stimulation Ablation Equivalence Trial. Strategies of radioiodine ablation in patients with low-risk thyroid cancer. N Engl J Med. 2012 May 3;366(18):1663-73. [https://doi.org/10.1056/NEJMoa1108586 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22551127/ PubMed] [https://clinicaltrials.gov/study/NCT00435851 NCT00435851]
-## '''Update:''' Schlumberger M, Leboulleux S, Catargi B, Deandreis D, Zerdoud S, Bardet S, Rusu D, Godbert Y, Buffet C, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Toubert ME, Kelly A, Benhamou E, Borget I. Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial. Lancet Diabetes Endocrinol. 2018 Aug;6(8):618-626. Epub 2018 May 26. [https://doi.org/10.1016/S2213-8587(18)30113-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/29807824 PubMed]
+## '''Update:''' Schlumberger M, Leboulleux S, Catargi B, Deandreis D, Zerdoud S, Bardet S, Rusu D, Godbert Y, Buffet C, Schvartz C, Vera P, Morel O, Benisvy D, Bournaud C, Toubert ME, Kelly A, Benhamou E, Borget I. Outcome after ablation in patients with low-risk thyroid cancer (ESTIMABL1): 5-year follow-up results of a randomised, phase 3, equivalence trial. Lancet Diabetes Endocrinol. 2018 Aug;6(8):618-626. Epub 2018 May 26. [https://doi.org/10.1016/S2213-8587(18)30113-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/29807824/ PubMed]
-# '''HiLo:''' Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012 May 3;366(18):1674-85. [https://doi.org/10.1056/NEJMoa1109589 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22551128 PubMed] NCT00415233
+# '''HiLo:''' Mallick U, Harmer C, Yap B, Wadsley J, Clarke S, Moss L, Nicol A, Clark PM, Farnell K, McCready R, Smellie J, Franklyn JA, John R, Nutting CM, Newbold K, Lemon C, Gerrard G, Abdel-Hamid A, Hardman J, Macias E, Roques T, Whitaker S, Vijayan R, Alvarez P, Beare S, Forsyth S, Kadalayil L, Hackshaw A. Ablation with low-dose radioiodine and thyrotropin alfa in thyroid cancer. N Engl J Med. 2012 May 3;366(18):1674-85. [https://doi.org/10.1056/NEJMoa1109589 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22551128/ PubMed] [https://clinicaltrials.gov/study/NCT00415233 NCT00415233]
-#'''ASTRA:''' Ho AL, Dedecjus M, Wirth LJ, Tuttle RM, Inabnet WB 3rd, Tennvall J, Vaisman F, Bastholt L, Gianoukakis AG, Rodien P, Paschke R, Elisei R, Viola D, So K, Carroll D, Hovey T, Thakre B, Fagin JA; ASTRA investigator group. Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA). J Clin Oncol. 2022 Jun 10;40(17):1870-1878. Epub 2022 Feb 22. [https://doi.org/10.1200/jco.21.00714 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35192411/ PubMed] NCT01843062
+#'''ASTRA:''' Ho AL, Dedecjus M, Wirth LJ, Tuttle RM, Inabnet WB 3rd, Tennvall J, Vaisman F, Bastholt L, Gianoukakis AG, Rodien P, Paschke R, Elisei R, Viola D, So K, Carroll D, Hovey T, Thakre B, Fagin JA; ASTRA investigator group. Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA). J Clin Oncol. 2022 Jun 10;40(17):1870-1878. Epub 2022 Feb 22. [https://doi.org/10.1200/jco.21.00714 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9851689/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35192411/ PubMed] [https://clinicaltrials.gov/study/NCT01843062 NCT01843062]
-#'''ESTIMABL2:''' Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L, Dygai I, Vera P, Rusu D, Schneegans O, Benisvy D, Klein M, Roux J, Eberle MC, Bastie D, Nascimento C, Giraudet AL, Le Moullec N, Bardet S, Drui D, Roudaut N, Godbert Y, Morel O, Drutel A, Lamartina L, Schvartz C, Velayoudom FL, Schlumberger MJ, Leenhardt L, Borget I. Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer. N Engl J Med. 2022 Mar 10;386(10):923-932. [https://doi.org/10.1056/nejmoa2111953 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35263518/ PubMed] NCT01837745
+#'''ESTIMABL2:''' Leboulleux S, Bournaud C, Chougnet CN, Zerdoud S, Al Ghuzlan A, Catargi B, Do Cao C, Kelly A, Barge ML, Lacroix L, Dygai I, Vera P, Rusu D, Schneegans O, Benisvy D, Klein M, Roux J, Eberle MC, Bastie D, Nascimento C, Giraudet AL, Le Moullec N, Bardet S, Drui D, Roudaut N, Godbert Y, Morel O, Drutel A, Lamartina L, Schvartz C, Velayoudom FL, Schlumberger MJ, Leenhardt L, Borget I. Thyroidectomy without Radioiodine in Patients with Low-Risk Thyroid Cancer. N Engl J Med. 2022 Mar 10;386(10):923-932. [https://doi.org/10.1056/nejmoa2111953 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35263518/ PubMed] [https://clinicaltrials.gov/study/NCT01837745 NCT01837745]
 ==Radioiodine & Selumetinib {{#subobject:29y7ur|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 273: / Line 141: @@
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
@@ Line 283: / Line 151: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Radiotherapy====
-*[[Iodine-131]]
+*[[Iodine-131]] (dose not specified)
 ====Targeted therapy====
-*[[Selumetinib (Koselugo)]]
+*[[Selumetinib (Koselugo)]] 75 mg PO twice per day on days 1 to 28
+'''4-week course'''
 </div></div>
 ===References===
-# '''MSK 09-048:''' Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Domínguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013 Feb 14;368(7):623-32. [https://doi.org/10.1056/NEJMoa1209288 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3615415/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23406027 PubMed] NCT00970359
+# '''MSK 09-048:''' Ho AL, Grewal RK, Leboeuf R, Sherman EJ, Pfister DG, Deandreis D, Pentlow KS, Zanzonico PB, Haque S, Gavane S, Ghossein RA, Ricarte-Filho JC, Domínguez JM, Shen R, Tuttle RM, Larson SM, Fagin JA. Selumetinib-enhanced radioiodine uptake in advanced thyroid cancer. N Engl J Med. 2013 Feb 14;368(7):623-32. [https://doi.org/10.1056/NEJMoa1209288 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc3615415/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23406027/ PubMed] [https://clinicaltrials.gov/study/NCT00970359 NCT00970359]
-==Sorafenib monotherapy {{#subobject:36a6b4|Regimen=1}}==
+=Advanced or metastatic disease, radioactive iodine-refractory=
+==Apatinib monotherapy {{#subobject:7hgub6|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:237686|Variant=1}}===
+===Regimen {{#subobject:afjug7|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366116/ Brose et al. 2014 (DECISION)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8678901/ Lin et al. 2022 (REALITY)]
-{| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|2017-2020
-|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-136-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
+| style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint)<br>Median OS: NYR vs 29.9 mo<br>(HR 0.42, 95% CI 0.18-0.97)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Apatinib (Aitan)]] 500 mg PO once per day on days 1 to 28
+'''28-day cycles'''
+</div></div>
+===References===
+#'''REALITY:''' Lin Y, Qin S, Li Z, Yang H, Fu W, Li S, Chen W, Gao Z, Miao W, Xu H, Zhang Q, Zhao X, Bao J, Li L, Ren Y, Lin C, Jing S, Ma Q, Liang J, Chen G, Zhang H, Zhang Y, Zhou X, Sang Y, Hou Z. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer: The REALITY Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):242-250. [https://doi.org/10.1001/jamaoncol.2021.6268 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8678901/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34913959/ PubMed] [https://clinicaltrials.gov/study/NCT03048877 NCT03048877]
+==Cabozantinib monotherapy {{#subobject:1dgac6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, pediatric dosing {{#subobject:1gacnd|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+''Note: this is the FDA-recommended dose in pediatric patients who are 12 years of age or older with BSA less than 1.2 m<sup>2</sup>.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Cabozantinib (Cometriq)]] 40 mg PO once per day
+'''Continued indefinitely'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2 {{#subobject:1hzndd|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
 |-
 |}
-|2009-2011
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00332-6 Brose et al. 2021 (COSMIC-311)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-302-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
+|-
+|} -->
+|2019-02-27 to 2020-08-18
 | style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Placebo|Placebo]]
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 10.8 vs 5.8 mo<br>(HR 0.59, 95% CI 0.45-0.76)
+| style="background-color:#1a9850" |Superior PFS (co-primary endpoint)<br>Median PFS: NYR vs 1.9 mo<br>(HR 0.22, 96% CI 0.13-0.36)
 |-
 |}
+''Note: this is the FDA-recommended dose for adult patients.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Sorafenib (Nexavar)]] 400 mg PO twice per day
+*[[Cabozantinib (Cometriq)]] 60 mg PO once per day on days 1 to 28
-'''Continued indefinitely'''
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''DECISION:''' Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Peña C, Molnár I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. Epub 2014 Apr 24. [https://doi.org/10.1016/s0140-6736(14)60421-9 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24768112 PubMed] NCT00984282
+# '''COSMIC-311:''' Brose MS, Robinson B, Sherman SI, Krajewska J, Lin CC, Vaisman F, Hoff AO, Hitre E, Bowles DW, Hernando J, Faoro L, Banerjee K, Oliver JW, Keam B, Capdevila J. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2021 Aug;22(8):1126-1138. Epub 2021 Jul 5. [https://doi.org/10.1016/s1470-2045(21)00332-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34237250/ PubMed] [https://clinicaltrials.gov/study/NCT03690388 NCT03690388]
+==Donafenib monotherapy {{#subobject:u7r1ca|Regimen=1}}==
-==Vandetanib monotherapy {{#subobject:83e502|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d2f77d|Variant=1}}===
+===Regimen {{#subobject:44trcd|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/S1470-2045(12)70335-2 Leboulleux et al. 2012 (D4200C00079)]
+|[https://doi.org/10.1158/1078-0432.ccr-22-3613 Lin et al. 2023 (ZGDD3)]
-|2007-2008
+|2018-08-29 to 2021-02-28
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo|Placebo]]
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
-| style="background-color:#1a9850" |Superior PFS
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 12.9 vs 6.4 mo<br>(HR 0.39, 95% CI 0.25-0.61)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Vandetanib (Caprelsa)]] 300 mg PO once per day
+*[[Donafenib (Zepsun)]] 300 mg PO twice per day on days 1 to 28
-'''Continued indefinitely'''
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''D4200C00079:''' Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gómez JM, Bonichon F, Leenhardt L, Soufflet C, Licour M, Schlumberger MJ. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012 Sep;13(9):897-905. Epub 2012 Aug 14. [https://doi.org/10.1016/S1470-2045(12)70335-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22898678 PubMed] NCT00537095
+#'''ZGDD3:''' Lin Y, Qin S, Yang H, Shi F, Yang A, Han X, Liu B, Li Z, Ji Q, Tang L, Deng Z, Ding Y, Fu W, Xie X, Li L, He X, Lv Z, Ma Q, Shen Z, Guo Z, Chen Z, Cui Y, Tan J, Gao Z, Jing S, Lu K, Luo X, Zhang Y, Fang Y, Li Z, Cheng Y, Lei S, Luan S, Chen G, Wang G, Wu L, Liu L. Multicenter Randomized Double-Blind Phase III Trial of Donafenib in Progressive Radioactive Iodine-Refractory Differentiated Thyroid Cancer. Clin Cancer Res. 2023 Aug 1;29(15):2791-2799. [https://doi.org/10.1158/1078-0432.ccr-22-3613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/37184934/ PubMed] [https://clinicaltrials.gov/study/NCT03602495 NCT03602495]
-=Advanced or metastatic disease=
-==Apatinib monotherapy {{#subobject:7hgub6|Regimen=1}}==
+==Lenvatinib monotherapy {{#subobject:PYR1|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:afjug7|Variant=1}}===
+===Regimen {{#subobject:PYV1|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 20%"|Dates of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 20%"|Comparator
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8678901/ Lin et al. 2022 (REALITY)]
+|[https://doi.org/10.1056/NEJMoa1406470 Schlumberger et al. 2015 (SELECT)]
-|2017-2020
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-135-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
+|-
+|} -->
+|2011-08-05 to 2012-10-04
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 18.3 vs 3.6 mo<br>(HR 0.21, 99% CI 0.14-0.31)
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401493/ Zheng et al. 2021 (E7080-C086-308)]
+|2017-NR
 | style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Placebo_88|Placebo]]
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
-| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: NYR vs 29.9 mo<br>(HR 0.42, 95% CI 0.18-0.97)
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 23.9 vs 3.7 mo<br>(HR 0.16, 95% CI 0.10-0.26)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Apatinib (Aitan)]] 500 mg PO once per day
+*[[Lenvatinib (Lenvima)]] 24 mg PO once per day on days 1 to 28
 '''28-day cycles'''
+</div>
+<div class="toccolours" style="background-color:#fff2ae">
+====Dose and schedule modifications====
+*Per the package insert, patients with eGFR of less than 30 mL/min/1.73m<sup>2</sup> by Cockroft-Gault or Child-Pugh C severe hepatic impairment should receive 14 mg PO once per day.
 </div></div>
 ===References===
-#'''REALITY:''' Lin Y, Qin S, Li Z, Yang H, Fu W, Li S, Chen W, Gao Z, Miao W, Xu H, Zhang Q, Zhao X, Bao J, Li L, Ren Y, Lin C, Jing S, Ma Q, Liang J, Chen G, Zhang H, Zhang Y, Zhou X, Sang Y, Hou Z. Apatinib vs Placebo in Patients With Locally Advanced or Metastatic, Radioactive Iodine-Refractory Differentiated Thyroid Cancer: The REALITY Randomized Clinical Trial. JAMA Oncol. 2022 Feb 1;8(2):242-250. [https://doi.org/10.1001/jamaoncol.2021.6268 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8678901/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34913959/ PubMed] NCT03048877
+<!-- # '''Abstract:''' Martin Schlumberger, Makoto Tahara, Lori J. Wirth, Bruce Robinson, Marcia S. Brose, Rossella Elisei, Corina E. Dutcus, Begoña de las Heras, Junming Zhu, Mouhammed Amir Habra, Kate Newbold, Manisha H. Shah, Ana O. Hoff, Andrew G Gianoukakis, Naomi Kiyota, Matthew Hiram Taylor, Sung-Bae Kim, Monika K Krzyzanowska, Steven I. Sherman. A phase 3, multicenter, double-blind, placebo-controlled trial of lenvatinib (E7080) in patients with 131I-refractory differentiated thyroid cancer (SELECT). 2014 ASCO Annual Meeting abstract LBA6008. [http://meetinglibrary.asco.org/content/132694-144 link to abstract] -->
-==Axitinib monotherapy {{#subobject:73fcb6|Regimen=1}}==
+# '''SELECT:''' Schlumberger M, Tahara M, Wirth LJ, Robinson B, Brose MS, Elisei R, Habra MA, Newbold K, Shah MH, Hoff AO, Gianoukakis AG, Kiyota N, Taylor MH, Kim SB, Krzyzanowska MK, Dutcus CE, de las Heras B, Zhu J, Sherman SI. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015 Feb 12;372(7):621-30. [https://doi.org/10.1056/NEJMoa1406470 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25671254/ PubMed] [https://clinicaltrials.gov/study/NCT01321554 NCT01321554]
+#'''E7080-C086-308:''' Zheng X, Xu Z, Ji Q, Ge M, Shi F, Qin J, Wang F, Chen G, Zhang Y, Huang R, Tan J, Huang T, Li S, Lv Z, Lin Y, Guo Z, Kubota T, Suzuki T, Ikezawa H, Gao M. A Randomized, Phase III Study of Lenvatinib in Chinese Patients with Radioiodine-Refractory Differentiated Thyroid Cancer. Clin Cancer Res. 2021 Oct 15;27(20):5502-5509. Epub 2021 Jul 29. [https://doi.org/10.1158/1078-0432.ccr-21-0761 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9401493/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34326132/ PubMed] [https://clinicaltrials.gov/study/NCT02966093 NCT02966093]
+==Pazopanib monotherapy {{#subobject:4ee26c|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:aff447|Variant=1}}===
+===Regimen {{#subobject:8faae3|Variant=1}}===
 {| class="wikitable sortable" style="width: 60%; text-align:center;"
 !style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
+!style="width: 33%"|Dates of enrollment
 !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1002/cncr.28766 Locati et al. 2014 (A4061027)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107731/ Bible et al. 2010 (MC057H)]
-|2006-2008
+|2008-2009
 | style="background-color:#91cf61" |Phase 2
 |-
@@ Line 382: / Line 312: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Axitinib (Inlyta)]] 5 mg PO twice per day
+*[[Pazopanib (Votrient)]] 800 mg PO once per day on days 1 to 28
-'''Continued indefinitely'''
+'''28-day cycles'''
+</div></div>
+===References===
+# '''MC057H:''' Bible KC, Suman VJ, Molina JR, Smallridge RC, Maples WJ, Menefee ME, Rubin J, Sideras K, Morris JC 3rd, McIver B, Burton JK, Webster KP, Bieber C, Traynor AM,  Flynn PJ, Goh BC, Tang H, Ivy SP, Erlichman C; Endocrine Malignancies Disease Oriented Group; Mayo Clinic Cancer Center; Mayo Phase 2 Consortium. Efficacy of pazopanib in progressive, radioiodine-refractory, metastatic differentiated thyroid cancers: results of a phase 2 consortium study. Lancet Oncol. 2010 Oct;11(10):962-72. Epub 2010 Sep 17. [https://doi.org/10.1016/s1470-2045(10)70203-5 link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3107731/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20851682/ PubMed] [https://clinicaltrials.gov/study/NCT00625846 NCT00625846]
+==Sorafenib monotherapy {{#subobject:36a6b4|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:237686|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366116/ Brose et al. 2014 (DECISION)]
+<!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26"
+|'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-136-1 <span style="color:white;">ESMO-MCBS (2)</span>]'''
+|-
+|} -->
+|2009-2011
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 10.8 vs 5.8 mo<br>(HR 0.59, 95% CI 0.45-0.76)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Sorafenib (Nexavar)]] 400 mg PO twice per day on days 1 to 28
+'''28-day cycles'''
 </div></div>
 ===References===
-# '''A4061027:''' Locati LD, Licitra L, Agate L, Ou SH, Boucher A, Jarzab B, Qin S, Kane MA, Wirth LJ, Chen C, Kim S, Ingrosso A, Pithavala YK, Bycott P, Cohen EE. Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer. 2014 Sep 1;120(17):2694-703. Epub 2014 May 20. [https://doi.org/10.1002/cncr.28766 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24844950 PubMed] NCT00389441
+# '''DECISION:''' Brose MS, Nutting CM, Jarzab B, Elisei R, Siena S, Bastholt L, de la Fouchardiere C, Pacini F, Paschke R, Shong YK, Sherman SI, Smit JW, Chung J, Kappeler C, Peña C, Molnár I, Schlumberger MJ; DECISION investigators. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 3 trial. Lancet. 2014 Jul 26;384(9940):319-28. Epub 2014 Apr 24. [https://doi.org/10.1016/s0140-6736(14)60421-9 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4366116/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/24768112/ PubMed] [https://clinicaltrials.gov/study/NCT00984282 NCT00984282]
 ==Sunitinib monotherapy {{#subobject:8d6c5|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
@@ Line 392: / Line 351: @@
 {| class="wikitable sortable" style="width: 80%; text-align:center;"
 !style="width: 25%"|Study
-!style="width: 25%"|Years of enrollment
+!style="width: 25%"|Dates of enrollment
 !style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
 !style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
@@ Line 404: / Line 363: @@
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Targeted therapy====
-*[[Sunitinib (Sutent)]] 37.5 mg PO once per day
+*[[Sunitinib (Sutent)]] 37.5 mg PO once per day on days 1 to 42
+'''42-day cycles'''
+</div></div>
+===References===
+# Carr LL, Mankoff DA, Goulart BH, Eaton KD, Capell PT, Kell EM, Bauman JE, Martins RG. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res. 2010 Nov 1;16(21):5260-8. Epub 2010 Sep 16. [https://doi.org/10.1158/1078-0432.CCR-10-0994 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063514/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20847059/ PubMed]
+==Vandetanib monotherapy {{#subobject:83e502|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:d2f77d|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
+!style="width: 20%"|Dates of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045(12)70335-2 Leboulleux et al. 2012 (D4200C00079)]
+|2007-2008
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|[[Thyroid cancer, differentiated - null regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS (primary endpoint)<br>Median PFS: 11.1 vs 5.9 mo<br>(HR 0.63, 60% CI 0.54-0.74)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Vandetanib (Caprelsa)]] 300 mg PO once per day
+'''Continued indefinitely'''
+</div></div>
+===References===
+# '''D4200C00079:''' Leboulleux S, Bastholt L, Krause T, de la Fouchardiere C, Tennvall J, Awada A, Gómez JM, Bonichon F, Leenhardt L, Soufflet C, Licour M, Schlumberger MJ. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: a randomised, double-blind, phase 2 trial. Lancet Oncol. 2012 Sep;13(9):897-905. Epub 2012 Aug 14. [https://doi.org/10.1016/S1470-2045(12)70335-2 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22898678/ PubMed] [https://clinicaltrials.gov/study/NCT00537095 NCT00537095]
+=Advanced or metastatic disease, all lines of therapy=
+==Axitinib monotherapy {{#subobject:73fcb6|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:aff447|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Dates of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[https://doi.org/10.1002/cncr.28766 Locati et al. 2014 (A4061027)]
+|2006-2008
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Targeted therapy====
+*[[Axitinib (Inlyta)]] 5 mg PO twice per day
 '''Continued indefinitely'''
 </div></div>
 ===References===
-# Carr LL, Mankoff DA, Goulart BH, Eaton KD, Capell PT, Kell EM, Bauman JE, Martins RG. Phase II study of daily sunitinib in FDG-PET-positive, iodine-refractory differentiated thyroid cancer and metastatic medullary carcinoma of the thyroid with functional imaging correlation. Clin Cancer Res. 2010 Nov 1;16(21):5260-8. Epub 2010 Sep 16. [https://doi.org/10.1158/1078-0432.CCR-10-0994 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3063514/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20847059 PubMed]
+# '''A4061027:''' Locati LD, Licitra L, Agate L, Ou SH, Boucher A, Jarzab B, Qin S, Kane MA, Wirth LJ, Chen C, Kim S, Ingrosso A, Pithavala YK, Bycott P, Cohen EE. Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and quality-of-life assessments. Cancer. 2014 Sep 1;120(17):2694-703. Epub 2014 May 20. [https://doi.org/10.1002/cncr.28766 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24844950/ PubMed] [https://clinicaltrials.gov/study/NCT00389441 NCT00389441]
 [[Category:Thyroid cancer regimens]]
-[[Category:Disease-specific pages]]
+[[Category:Histology-specific pages]]
 [[Category:Endocrine cancers]]
 [[Category:Head and neck cancers]]

Difference between revisions of "Thyroid cancer, differentiated"

Latest revision as of 17:51, 23 June 2024

Guidelines

ATA

ESMO

NCCN

Adjuvant therapy

Radioiodine ablation

Regimen variant #1, 1.1 GBq

Preceding treatment

Radiotherapy

Regimen variant #2, 3.7 GBq

Preceding treatment

Radiotherapy

Regimen variant #3, variable

Preceding treatment

Radiotherapy

References

Radioiodine & Selumetinib

Regimen

Radiotherapy

Targeted therapy

References

Advanced or metastatic disease, radioactive iodine-refractory

Apatinib monotherapy

Regimen

Targeted therapy

References

Cabozantinib monotherapy

Regimen variant #1, pediatric dosing

Targeted therapy

Regimen variant #2

Targeted therapy

References

Donafenib monotherapy

Regimen

Targeted therapy

References

Lenvatinib monotherapy

Regimen

Targeted therapy

Dose and schedule modifications

References

Pazopanib monotherapy

Regimen

Targeted therapy

References

Sorafenib monotherapy

Regimen

Targeted therapy

References

Sunitinib monotherapy

Regimen

Targeted therapy

References

Vandetanib monotherapy

Regimen

Targeted therapy

References

Advanced or metastatic disease, all lines of therapy

Axitinib monotherapy

Regimen

Targeted therapy

References

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