Thyroid cancer, medullary
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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.
Last updated on 2024-07-23: 8 regimens on this page
9 variants on this page
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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.
ESMO
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Thyroid Carcinoma.
- 2010: Tuttle et al. Medullary carcinoma. PubMed
Advanced or metastatic disease, iodine-refractory
Axitinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Locati et al. 2014 (A4061027) | 2006-2008 | Phase 2 |
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 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) |
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 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
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 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-RT-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
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 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
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 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
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 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
- 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 PubMed 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 PubMed 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 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
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
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 PubMed
- 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 PubMed 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 PubMed NCT00410761