Thyroid cancer, medullary

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For placebo or observational studies in this condition, please visit this page.
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Note: these are regimens tested in histology-specific populations, please see the main thyroid cancer page for other regimens.
Last updated on 2024-07-23:8 regimens on this page
9 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 for the management of medullary thyroid carcinoma EuroPMC
==ESMO==
*2019: Filetti et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
*2012: Pacini et al. Thyroid cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
==NCCN==
*NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Thyroid Carcinoma.
*2010: Tuttle et al. Medullary carcinoma. EuroPMC
=Advanced or metastatic disease, iodine-refractory=
==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 dosing details in manuscript have been reviewed by our editors EuroPMC NCT00389441
==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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
=Locally advanced or metastatic disease, targeted therapy-naive=
==Cabozantinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hadoux et al. 2023 (LIBRETTO-531)	2020-02 to 2023-03 	Phase 3 (C)	Selpercatinib	Shorter PFS (primary endpoint)Median PFS: 16.8 vs NYR mo(HR 3.57, 95% CI 2.08-6.25)
====Biomarker eligibility criteria====
*RET mutation
====Targeted therapy====
*Cabozantinib (Cometriq) 140 mg PO once per day
Continued indefinitely
===References===
#LIBRETTO-531: Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Führer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04211337
==Selpercatinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hadoux et al. 2023 (LIBRETTO-531)	2020-02 to 2023-03 	Phase 3 (E-RT-switch-ic)	1a. Cabozantinib1b. Vandetanib	Longer PFS (primary endpoint)Median PFS: NYR vs 16.8 mo(HR 0.28, 95% CI 0.16-0.48)
====Biomarker eligibility criteria====
*RET mutation
====Targeted therapy====
*Selpercatinib (Retevmo) 160 mg PO twice per day
Continued indefinitely
===References===
#LIBRETTO-531: Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Führer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04211337
==Sorafenib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Lam et al. 2010 (OSU 06054)	2006-2008 	Phase 2
====Prior treatment criteria====
*No prior targeted therapy with sorafenib, vandetanib, or motesanib
====Targeted therapy====
*Sorafenib (Nexavar) 400 mg PO twice per day on days 1 to 28
28-day cycles
===References===
# OSU 06054: Lam ET, Ringel MD, Kloos RT, Prior TW, Knopp MV, Liang J, Sammet S, Hall NC, Wakely PE Jr, Vasko VV, Saji M, Snyder PJ, Wei L, Arbogast D, Collamore M, Wright JJ, Moley JF, Villalona-Calero MA, Shah MH. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010 May 10;28(14):2323-30. Epub 2010 Apr 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00390325
==Vandetanib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Hadoux et al. 2023 (LIBRETTO-531)	2020-02 to 2023-03 	Phase 3 (C)	Selpercatinib	Shorter PFS (primary endpoint)Median PFS: 16.8 vs NYR mo(HR 3.57, 95% CI 2.08-6.25)
====Biomarker eligibility criteria====
*RET mutation
====Targeted therapy====
*Vandetanib (Caprelsa) 300 mg PO once per day
Continued indefinitely
===References===
#LIBRETTO-531: Hadoux J, Elisei R, Brose MS, Hoff AO, Robinson BG, Gao M, Jarzab B, Isaev P, Kopeckova K, Wadsley J, Führer D, Keam B, Bardet S, Sherman EJ, Tahara M, Hu MI, Singh R, Lin Y, Soldatenkova V, Wright J, Lin B, Maeda P, Capdevila J, Wirth LJ; LIBRETTO-531 Trial Investigators. Phase 3 Trial of Selpercatinib in Advanced RET-Mutant Medullary Thyroid Cancer. N Engl J Med. 2023 Nov 16;389(20):1851-1861. Epub 2023 Oct 21. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT04211337
=Locally advanced or metastatic disease, subsequent lines of therapy=
==Cabozantinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Kurzrock et al. 2011 (XL184-001)	2005-2008 	Non-randomized 	 	
Elisei et al. 2013 (EXAM) 	2008-2011 	Phase 3 (E-RT-esc)	Placebo 	Longer PFS (primary endpoint)Median PFS: 11.2 vs 4 mo(HR 0.28, 95% CI 0.19-0.40)Did not meet secondary endpoint of OSMedian OS: 26.6 vs 21.1 mo(HR 0.85, 95% CI 0.64-1.12)
====Targeted therapy====
*Cabozantinib (Cometriq) 140 mg PO once per day, taken at least 2 hours before or 1 hour after meals
Continued indefinitely
===References===
# XL184-001: Kurzrock R, Sherman SI, Ball DW, Forastiere AA, Cohen RB, Mehra R, Pfister DG, Cohen EE, Janisch L, Nauling F, Hong DS, Ng CS, Ye L, Gagel RF, Frye J, Müller T, Ratain MJ, Salgia R. Activity of XL184 (Cabozantinib), an oral tyrosine kinase inhibitor, in patients with medullary thyroid cancer. J Clin Oncol. 2011 Jul 1;29(19):2660-6. Epub 2011 May 23. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00215605
# EXAM: Elisei R, Schlumberger MJ, Müller SP, Schöffski P, Brose MS, Shah MH, Licitra L, Jarzab B, Medvedev V, Kreissl MC, Niederle B, Cohen EE, Wirth LJ, Ali H, Hessel C, Yaron Y, Ball D, Nelkin B, Sherman SI. Cabozantinib in progressive medullary thyroid cancer. J Clin Oncol. 2013 Oct 10;31(29):3639-46. Epub 2013 Sep 3. Erratum in: J Clin Oncol. 2014 Jun 10;32(17):1864. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00704730
## Update: Schlumberger M, Elisei R, Müller S, Schöffski P, Brose M, Shah M, Licitra L, Krajewska J, Kreissl MC, Niederle B, Cohen EEW, Wirth L, Ali H, Clary DO, Yaron Y, Mangeshkar M, Ball D, Nelkin B, Sherman S. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol. 2017 Nov 1;28(11):2813-2819. link to original article link to PMC article EuroPMC
=All lines of therapy=
==Vandetanib monotherapy==
===Regimen variant #1, 100 mg/day===
Study 	Dates of enrollment	Evidence
Robinson et al. 2010 (D4200C00068)	2006-2007 	Phase 2, fewer than 20 patients
====Eligibility criteria====
*MEN2A, MEN2B, or familial MTC by either germline RET mutation or family history
====Targeted therapy====
*Vandetanib (Caprelsa) 100 mg PO once per day
Continued indefinitely
====Dose and schedule modifications====
*D4200C00068, at progression: eligible patients could increase the dose to 300 mg PO once per day; see paper for details
===Regimen variant #2, 300 mg/day===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Wells et al. 2010 	2004-2006 	Phase 2 	 	
Wells et al. 2011 (ZETA)	2006-12 to 2007-11 	Phase 3 (E-RT-esc)	Placebo 	Longer PFS (primary endpoint)Median PFS: NYR vs 19.3 mo(HR 0.46, 95% CI 0.31-0.69)
====Eligibility criteria====
*Wells et al. 2010: MEN2A, MEN2B, or familial MTC by either germline RET mutation or family history
====Targeted therapy====
*Vandetanib (Caprelsa) 300 mg PO once per day
Continued indefinitely
===References===
# Wells SA Jr, Gosnell JE, Gagel RF, Moley J, Pfister D, Sosa JA, Skinner M, Krebs A, Vasselli J, Schlumberger M. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol. 2010 Feb 10;28(5):767-72. Epub 2010 Jan 11. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
# D4200C00068: Robinson BG, Paz-Ares L, Krebs A, Vasselli J, Haddad R. Vandetanib (100 mg) in patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Endocrinol Metab. 2010 Jun;95(6):2664-71. Epub 2010 Apr 6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC content property of HemOnc.org NCT00358956
# ZETA: Wells SA Jr, Robinson BG, Gagel RF, Dralle H, Fagin JA, Santoro M, Baudin E, Elisei R, Jarzab B, Vasselli JR, Read J, Langmuir P, Ryan AJ, Schlumberger MJ. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial. J Clin Oncol. 2012 Jan 10;30(2):134-41. Epub 2011 Oct 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00410761
Category:Thyroid cancer regimens
Category:Histology-specific pages
Category:Endocrine cancers
Category:Head and neck cancers