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.

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 PubMed

ESMO

NCCN

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

Continued indefinitely

References

  1. 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

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

42-day cycles

References

  1. 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

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 Inferior PFS (primary endpoint)

Biomarker eligibility criteria

  • RET mutation

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed 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-switch-ic) 1a. Cabozantinib
1b. Vandetanib 		Superior 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

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed 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

28-day cycles

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed 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 Inferior PFS (primary endpoint)

Biomarker eligibility criteria

  • RET mutation

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript PubMed 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 Superior 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 OS
Median OS: 26.6 vs 21.1 mo
(HR 0.85, 95% CI 0.64-1.12)

Targeted therapy

Continued indefinitely

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed NCT00215605
  2. 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 contains dosing details in manuscript link to PMC article PubMed NCT00704730
    1. 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 PubMed

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

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 Superior 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

Continued indefinitely

References

  1. 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 contains dosing details in manuscript link to PMC article PubMed
  2. 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 contains dosing details in manuscript link to PMC article PubMed content property of HemOnc.org NCT00358956
  3. 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 contains dosing details in manuscript link to PMC article PubMed NCT00410761
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