Thyroid Carcinoma Treatment Regimens

Thyroid Carcinoma Treatment Regimens

Clinical Trials: The NCCN recommends cancer patient participation in clinical trials as the gold standard for treatment.

Cancer therapy selection, dosing, administration, and the management of related adverse events can be a complex process that should be handled by an experienced health care team. Clinicians must choose and verify treatment options based on the individual patient; drug dose modifications and supportive care interventions should be administered accordingly. The cancer treatment regimens below may include both U.S. Food and Drug Administration-approved and unapproved indications/regimens. These regimens are provided only to supplement the latest treatment strategies.

These Guidelines are a work in progress that may be refined as often as new significant data become available. The NCCN Guidelines® are a consensus statement of its authors regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply or consult any NCCN Guidelines® is expected to use independent medical judgment in the context of individual clinical circumstances to determine any patient’s care or treatment. The NCCN makes no warranties of any kind whatsoever regarding their content, use, or application and disclaims any responsibility for their application or use in any way.

Note: All recommendations are category 2A unless otherwise indicated.

▶Systemic Therapy for Thyroid Carcinoma1

REGIMEN

DOSING

Papillary Carcinomaa,b

Systemic Therapy For Locally Recurrent, Advanced, and/or Metastatic Disease Not Amenable to RAI Therapy

Axitinib2-4,c,d

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Cabozantinib6-9,c,d

Days 1-28: Cabozantinib 60-80mg (dose escalated based on response) orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Cabozantinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Dabrafenib (BRAF-positive)10-12c,d

Days 1-28: Dabrafenib 150mg orally twice daily.

Repeat cycle every 4 weeks.

Entrectinib13,14c-e (for patients with NTRK gene fusion-positive tumors)

Days 1-28: Entrectinib 600mg orally once daily.

Repeat cycle every 4 weeks.

Everolimus15-17,c,d

Days 1-28: Everolimus 10mg orally once daily.

Repeat cycle every 4 weeks.

Larotrectinib18,19c-e (for patients with NTRK gene fusion-positive tumors)

Days 1-28: Larotrectinib 100mg twice daily.

Repeat cycle every 4 weeks.

Lenvatinib (preferred for progressive and/or symptomatic disease)20-23,f

Days 1-28: Lenvatinib 24mg orally once daily.

Repeat cycle every 4 weeks.

Pazopanib24,25,c,d

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with tumor mutational burden [TMB]-high tumors with 10 mut/Mb or higher)26-28

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 week for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 42 days for up to 2 years.

Selpercatinib (for RET fusion-positive tumors)29-31

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Sorafenib (for progressive and/or symptomatic disease)32-34,f

Days 1-28: Sorafenib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Sunitinib35-38,c,d

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on- followed by 2 weeks off-treatment)

OR

Days 1-28: Sunitinib 37.5mg orally once daily.

Repeat cycle every 4 weeks.

Vandetinib39,40,c,d

Days 1-28: Vandetinib 300mg orally once daily.

Repeat cycle every 4 weeks.

Vemurafenib41,42,c,d

Days 1-28: Vemurafenib 960mg orally twice daily.

Repeat cycle every 4 weeks.

Follicular Carcinomab,g

Systemic Therapy For Treatment of Progressive and/or Symptomatic Locally Recurrent, Advanced, and/or Metastatic Disease Not Amenable to RAI Therapy

Axitinib2-5,c,d

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Cabozantinib6-9,c,d

Days 1-28: Cabozantinib 60-80mg (dose escalated based on response) orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Cabozantinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Dabrafenib (BRAF-positive)10-12,c,d

Days 1-28: Dabrafenib 150mg orally twice daily.

Repeat cycle every 4 weeks.

Entrectinib (for patients with NTRK gene fusion-positive tumors)13-17c-e

Days 1-28: Entrectinib 600mg orally once daily.

Repeat cycle every 4 weeks.

Everolimus15-17,c,d

Days 1-28: Everolimus 10mg orally once daily.

Repeat cycle every 4 weeks.

Larotrectinib (for patients with NTRK gene fusion-positive tumors)18,19,c-e

Days 1-28: Larotrectinib 100mg twice daily.

Repeat cycle every 4 weeks.

Lenvatinib (preferred for progressive and/or symptomatic disease)20-23,f

Days 1-28: Lenvatinib 24mg once daily.

Repeat cycle every 4 weeks.

Pazopanib24,25,c,d

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with tumor mutational burden [TMB]-high tumors with 10 mut/Mb or higher)26-28

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 week for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 42 days for up to 2 years.

Selpercatinib (for RET fusion-positive tumors)29-31

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Sorafenib (for progressive and/or symptomatic disease)32-34,f

Days 1-28: Sorafenib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Sunitinib35-38,c,d

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on- followed by 2 weeks off-treatment)

OR

Days 1-28: Sunitinib 37.5mg orally once daily.

Repeat cycle every 4 weeks.

Vandetinib39,40,c,d

Days 1-28: Vandetinib 300mg orally once daily.

Repeat cycle every 4 weeks.

Vemurafenib (BRAF-positive)41,42,c,d

Days 1-28: Vemurafenib 960mg orally twice daily.

Repeat cycle every 4 weeks.

Hürthle Cell Carcinomab,h

Systemic Therapy For Treatment of Progressive and/or Symptomatic Locally Recurrent, Advanced, and/or Metastatic Disease Not Amenable to RAI Therapy

Axitinib2-5,c,d

Days 1-28: Axitinib 5-10mg orally twice daily.

Repeat cycle every 4 weeks.

Cabozantinib6-9,c,d

Days 1-28: Cabozantinib 60-80mg (dose escalated based on response) orally once daily.

Repeat cycle every 4 weeks.

OR

Days 1-28: Cabozantinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Dabrafenib (BRAF-positive)10-12,c,d

Days 1-28: Dabrafenib 150mg orally twice daily.

Repeat cycle every 4 weeks.

Entrectinib (for patients with NTRK gene fusion-positive tumors)13,14,c-e

Days 1-28: Dabrafenib 150mg orally once daily.

Repeat cycle every 4 weeks.

Everolimus15-17,c,d

Days 1-28: Everolimus 10mg orally once daily.

Repeat cycle every 4 weeks.

Larotrectinib (for patients with NTRK gene fusion-positive tumors)18,19c-e

Days 1-28: Larotrectinib 100mg twice daily.

Repeat cycle every 4 weeks.

Lenvatinib (preferred for progressive and/or symptomatic disease)20-23,f

Days 1-28: Lenvatinib 24mg once daily.

Repeat cycle every 4 weeks.

Pazopanib24,25,c,d

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with tumor mutational burden [TMB]-high tumors with 10 mut/Mb or higher)26-28

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 weeks for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 42 days for up to 2 years.

Selpercatinib (for RET fusion-positive tumors)29-31

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Sorafenib (for progressive and/or symptomatic disease)32-34,f

Days 1-28: Sorafenib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Sunitinib35-38,c,d

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on- followed by 2 weeks off-treatment)

OR

Days 1-28: Sunitinib 37.5mg orally once daily.

Repeat cycle every 4 weeks.

Vandetinib39,40,c,d

Days 1-28: Vandetinib 300mg orally once daily.

Repeat cycle every 4 weeks.

Vemurafenib (BRAF-positive)41,42,c,d

Days 1-28: Vemurafenib 960mg orally twice daily.

Repeat cycle every 4 weeks.

Medullary Carcinomab

Systemic Therapy For Treatment of Locoregional Recurrent or Persistent Disease

Preferred

Cabozantinib (Category 1)9,43,44,d,i

Days 1-28: Cabozantinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Selpercatinib (for RET fusion-positive tumors)29-31,d,i

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Vandetinib (Category 1)40,45,d,i,j

Days 1-28: Vandetinib 300mg orally once daily.

Repeat cycle every 4 weeks.

Systemic Therapy for Treatment of Recurrent or Persistent Distant Metastases

Asymptomatic Disease

Preferred

Cabozantinib (Category 1)9,43,44,d,i

Days 1-28: Cabozantinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Selpercatinib (for RET fusion-positive tumors)29-31

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Vandetinib (Category 1)40,45,i-k

Days 1-28: Vandetinib 300mg orally once daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Pembrolizumab (for patients with tumor mutational burden [TMB]-high tumors with 10 mut/Mb or higher)26-28

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 week for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 42 days for up to 2 years.

Symptomatic Disease or Progression

Preferred

Cabozantinib (Category 1)9,43,44,d,i

Days 1-28: Cabozantinib 140mg orally once daily.

Repeat cycle every 4 weeks.

Selpercatinib (for RET fusion-positive tumors)29-31

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Vandetinib (Category 1)40,45,i-k

Days 1-28: Vandetinib 300mg orally once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Doxorubicin + Streptozocin Alternating With Fluorouracil + Dacarbazine46,m

Day 1: Doxorubicin 60mg/m2 IV push

Days 1-5: Streptomycin 500mg/m2 IV push.

Administer for one 4-week cycle (odd cycle) alternating with one 4-week cycle (even cycle) of:

Days 1-5: Fluorouracil 400mg/m2 IV push

Days 1-5: Dacarbazine 200mg/m2 IV over 30 minutes.

Repeat alternating cycles until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Fluorouracil + Dacarbazine Alternating With Fluorouracil + Streptozocin47,m

Days 1-5: Fluorouracil 400mg/m2 IV push

Days 1-5: Dacarbazine 200mg/m2 IV over 30 minutes.

Administer for one 3-week cycle (odd cycle) alternating with one 3-week cycle (even cycle) of:

Days 1-5: Fluorouracil 400mg/m2 IV push

Days 1-5: Streptomycin 500mg/m2 IV push.

Repeat alternating cycles until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

Lenvatinib23,48,l

Days 1-28: Lenvatinib 24mg orally once daily.

Repeat cycle every 4 weeks.

Pazopanib24,25,l

Days 1-28: Pazopanib 800mg orally once daily.

Repeat cycle every 4 weeks.

Sorafenib34,37,49,50,l

Days 1-28: Sorafenib 400mg orally twice daily.

Repeat cycle every 4 weeks.

Sunitinib34-38,l

Days 1-28: Sunitinib 50mg orally once daily.

Repeat cycle every 6 weeks (4 weeks on- followed by 2 weeks off-treatment)

OR

Days 1-28: Sunitinib 37.5mg orally once daily.

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Pembrolizumab (for patients with tumor mutational burden [TMB]-high tumors with 10 mut/Mb or higher)26-28

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 week for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 42 days for up to 2 years.

Anaplastic Carcinoma

Adjuvant/Radiosensitizing Chemotherapy Regimens

Other Recommended Regimens

Cisplatin51,n

Days 1: Cisplatin 30-40mg/m2 IV over 60 minutes.

Repeat cycle weekly for 6 weeks with concurrent radiation

Docetaxel + Doxorubicin51

Day 1: Doxorubicin 20mg/m2 IV push

Day 1: Docetaxel 20mg/m2 IV over 60 minutes.

Repeat cycle weekly for 6 weeks with concurrent radiation.

OR

Day 1: Doxorubicin 60mg/m2 IV push

Day 1: Docetaxel 60mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks for 6 weeks with concurrent radiation (with pegfilgrastim)

Doxorubicin51

Days 1: Doxorubicin 20mg/m2 IV push.

Repeat cycle weekly for 6 weeks with concurrent radiation.

OR

Day 1: Doxorubicin 60mg/m2 IV push.

Repeat cycle every 3 weeks for 6 weeks with concurrent radiation.

Paclitaxel51

Days 1: Paclitaxel 30-60mg/m2 IV over 60 minutes.

Repeat cycle weekly with concurrent radiation.

Paclitaxel + Carboplatin51

Day 1: Paclitaxel 50mg/m2 IV over 1 hour, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat cycle weekly for 6 weeks with concurrent radiation.

Systemic Therapy for Metastatic Disease

Preferred

Dabrafenib + Trametinb (BRAF V600E mutation positive)52-54,o

Days 1-28: Dabrafenib 150mg orally twice daily

Days 1-12: Trametinib 2mg orally daily.

Repeat cycle every 4 weeks.

Entrectinib (for patients with NTRK gene fusion-positive tumors)13,14,c-e

Days 1-28: Entrectinib 600mg orally once daily.
Repeat cycle every 4 weeks

Larotrectinib (NTRK gene fusion positive)18,19

Days 1-28: Larotrectinib 100mg orally twice daily.

Repeat cycle every 4 weeks.

Selpercatinib (for RET fusion-positive tumors)29-31

Days 1-28: Selpercatinib 120mg (patients less than 50kg) orally twice daily.

Repeat cycle every 4 weeks.

Days 1-28: Selpercatinib 160mg (patients 50kg or higher) orally twice daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Docetaxel + Doxorubicin51

Day 1: Doxorubin 60mg/m2 IV push

Day 1: Docetaxel 60mg/m2 IV over 60 minutes.

Repeat cycle every 3-4 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose (with pegfilgrastim)

OR

Day 1: Doxorubicin 20mg/m2 IV push

Day 1: Docetaxel 20mg/m2 IV over 60 minutes.

Repeat cycle weekly for 6 weeks with concurrent radiation.

Doxorubicin51,55

Day 1: Doxorubicin 60-75mg/m2 IV push

Repeat cycle every 3 weeks until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose.

OR

Day 1: Doxorubicin 20mg/m2 IV push.

Repeat cycle weekly until disease progression or unacceptable toxicity including reaching a lifetime cumulative anthracycline dose

Paclitaxel51,56

Day 1: Paclitaxel 135-200mg/m2 IV over 3 hours

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 60-90mg/m2 IV over 60 minutes.

Repeat cycle weekly.

Paclitaxel + Carboplatin51,57

Day 1: Paclitaxel 135-175mg/m2 IV over 3 hours, followed by:

Day 1: Carboplatin AUC 5-6 IV over 30 minutes.

Repeat cycle every 3-4 weeks.

OR

Day 1: Paclitaxel 60-100mg/m2 IV, followed by:

Day 1: Carboplatin AUC 2 IV over 30 minutes.

Repeat cycle weekly.

Useful in Certain Circumstances

Levantinib23,58 (if not tolerating or no response to recommended agents in patients without curative option)

Days 1-28: Lenvatinib 24mg orally once daily.

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with tumor mutational burden [TMB]-high tumors with 10 mut/Mb or higher)26-28

Day 1: Pembrolizumab 200mg IV over 30 minutes.

Repeat cycle every 3 week for up to 2 years.

OR

Day 1: Pembrolizumab 400mg IV over 30 minutes.

Repeat cycle every 42 days for up to 2 years.

  a Primary treatment following surgery may involve consideration of levothyroxine therapy to keep thyroid stimulating hormone (TSH) low or normal. Consideration of post-thyroidectomy radioactive iodine (RAI) ablation and/or levothyroxine are recommended for some patients, and levothyroxine or RAI ablation are options for some patients with recurrent disease.

  b Cytotoxic chemotherapy has been shown to have minimal efficacy, although most studies were small and underpowered.

  c Commercially available small-molecule kinase inhibitors (such as axitinib, everolimus, pazopanib, sunitinib, vandetanib, vemurafenib [BRAF positive], dabrafenib [BRAF positive], or cabozantinib [all Category 2A]) can be considered if clinical trials are not available or appropriate.

  d Kinase inhibitor therapy may not be appropriate for patients with stable or slowly progressive indolent disease.

  e Larotrectinib and entrectinib are FDA-approved for patients with NTRK gene fusion-positive advanced solid tumors.

  f The decision of whether to use lenvatinib (preferred) or sorafenib should be individualized for each patient based on likelihood of response and comorbidities.

  g Primary treatment following surgery may involve consideration of levothyroxine therapy to keep TSH low or normal. Consideration of post-thyroidectomy RAI ablation is recommended for some patients, and levothyroxine or RAI ablation are options for some patients with recurrent disease.

  h Primary treatment following surgery may involve consideration of levothyroxine therapy to keep TSH low or normal. Consideration of post-thyroidectomy radioactive iodine (RAI) ablation and/or levothyroxine are recommended for some patients, including those with known or suspected distant metastatic disease. Levothyroxine or RAI ablation are options for some patients with recurrent disease.

  i Increasing tumor markers, in the absence of structural disease progression, are not an indication for treatment with systemic therapy.

  j Only health care professionals and pharmacies certified through the vandetinib Risk Evaluation and Mitigation Strategy (REMS) program, a restricted distribution program, will be able to prescribe and dispense the drug.

  k Treatment with systemic therapy is not recommended for increasing calcitonin/CEA alone.

  l While not FDA approved for treatment of medullary thyroid cancer, other commercially available small-molecule kinase inhibitors (such as sorafenib, sunitinib, lenvatinib, or pazopanib) can be considered if clinical trials, vandetinib or cabozantinib are not available or appropriate, or if the patient progresses on preferred systemic therapy options.

m Doxorubicin/streptozocin alternating with flurorouracil/dacarbazine or fluorouracil/decarbazine alternating with fluorouracil/streptozocin.

  n Hydration is required with supplemental electrolytes pre- and post-administration of Cisplatin.

  o Consider dabrafenib/trametinib if BRAF V600E mutation-positive (Subbiah V, et al. J Clin Oncol. 2018;36:7-13); larotrectinib or entrectinib if NTRK gene fusion-positive (Drilon A, et al. N Engl J Med. 2018;378:731-738; Doebele RC, et al. Lancet Oncol. 2020;21:271-282); selpetcatinib if RET gene fusion-positive (Wirth L, et al. Presented at the Annual Meeting of the European Society for Medical Oncology [ESMO] in Barcelona, Spain, September 27-October 1, 2019; Oral presentation) or pembrolizumab for TMB-H (Marabelle A, et al. Presented at the Annual Meeting of ESMO in Barcelona, Spain, September 30, 2019).

References

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  3. Locati LD, Licitra L, Agate L, et al. Treatment of advanced thyroid cancer with axitinib: Phase 2 study with pharmacokinetic/pharmacodynamic and ­quality-of- life assessments. Cancer. 2014;120:2694-29703.

  4. Cohen EEW, Rosen LS, Vokes EE, et al. Axitinib is an active treatment for all histologic subtypes of advanced thyroid cancer: Results from a phase II study. J Clin Oncol. 2008;26:4708-4713.

  5. Axitinib (Inlyta) [package insert] New York, NY: Pfizer Labs; 2020.

  6. Cabanillas ME, Brose MS, Holland J, et al. A phase I study of cabozantinib (XL184) in patients with differentiated thyroid cancer. Thyroid. 2014;24:1508-1514.

  7. Cabanillas ME, de Souza JA, Geyer S, et al. Cabozantinib As salvage therapy for patients with tyrosine kinase inhibitor-refractory differentiated thyroid cancer: Results of a multicenter phase II International Thyroid Oncology Group Trial. J Clin Oncol. 2017;35:3315-3321.

  8. Shah MH, de Souza J, Wirth L, et al. Cabozantinib in patients with radioiodine refractory differentiated thyroid cancer who progressed on prior VEGFR-targeted therapy: Results of NCI- and ITOG-sponsored multicenter phase II clinical trial. American Thyroid Association Annual Meeting. October 18-23, 2015. Lake Buena Vista, FL. Abstract 73.

  9. Cabozantinib (Cometriq) [package insert]. Alameda, CA: Exelixis, Inc.; 2020.

10. Falchook GS, Millward M, Hong D, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid. 2015;25:71-77.

11. Subbian V, Kreitman RJ, Wainberg ZA, et al. Dabrafenib and trametinib treatment in patients with locally advanced or metastatic BRAF V600-mutant anaplastic thyroid cancer. J Clin Oncol. 2018;36:7-13.

12. Dabrafenib (Tafinlar) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2019.

13. Drilon A, Siena S, Ou S-H I, et al. Safety and antitumor activity of the multitargeted pan-TRK, ROS1, and ALK inhibitor entrectinib: Combined results from two phase I trials (ALKA-372-001 and STARTRK-1). Cancer Discov. 2017;7:400-409.

14. Entrectinib (Rozlytrek) [package insert]. South San Francisco, CA: Genentech, Inc.; 2019.

15. Lim SM, Chang H, Yoon MJ, et al. A Multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes. Ann Oncol. 2013;24:3089-3094.

16. Schneider TC, de Wit D, Links TP, et al. Everolimus in patients with advanced follicular-­derived thyroid Cancer: Results of a phase II clinical trial. J Clin Endocrinol Metab. 2017;102:698-707.

17. Everolimus (Affinitor) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2020.

18. Drilon A, Laetsch TW, Kummar S, et al. Efficacy of larotrectinib in TRK fusion-positive cancers in adults and children. N Engl J Med. 2018;378:731-739.

19. Larotrectinib (Vitrakvi) [package insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; 2019.

20. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-­refractory thyroid cancer. N Engl J Med. 2015;372:621-630.

21. Cabanillas ME, Schlumberger M, Jarzab B, et al. A phase 2 trial of lenvatinib (E7080) in advanced, progressive, radioiodine-refractory, differentiated thyroid cancer: A clinical outcomes and biomarker assessment. Cancer. 2015;121:2749-2756.

22. Brose MS, Worden FP, Newbold KL, et al. Effect of age on the efficacy and safety of lenvatinib in radioiodine-refractory differentiated thyroid cancer in the phase III SELECT trial. J Clin Oncol. 2017;35:2692-2699.

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24. Bible KC, Suman VJ, Molina JR, et al. Efficacy of pazopanib in progressive, radioiodine-­refractory, metastatic differentiated thyroid cancers: Results of a phase 2 consortium study. Lancet Oncol. 2010;11:962-972.

25. Pazopanib (Votrient) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corp; 2017.

26. Marabelle A, Fakih MG, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with select advanced solid tumours treated with pembrolizumab in KEYNOTE-158. Ann Oncol. 2019;30 (suppl_30; abstr 1192O).

27. Lala M, Ruosi T, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modeling and simulation. Eur J Cancer. 2020;131:68-75.

28. Pembrolizumab {Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co, Inc.; 2020.

29. Wirth L, Sherman E, Drilon A, et al. Registrational results of LOXO-292 in patients with RET-altered thyroid cancers. Ann Oncol. 2019; 30(Suppl_5; abstr LBA93)

30. Shah MH, Sherman EJ, Robinson B, et al. Selpercatinib (LOXO-292) in patients with RET-mutant medullary thyroid cancer. J Clin Oncol. 2020;38(suppl; abstr 3594).

31. Selpercatinib (Retevmo) [package insert]. Indianapolis, IN: Eli Lilly and Co.; 2020.

32. Brose MS, Nutting CM, Jarzab B, et al. Sorafenib in radioactive iodine-refractory, locally advanced or metastatic differentiated thyroid cancer: A randomised, double-blind, phase 3 trial. Lancet. 2014;384:319-328.

33. Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009;27:1675-1684.

34. Sorafenib (Nexavar) [package insert]. Whippany, NJ: Bayer Healthcare Pharmaceuticals, Inc.; 2018.

35. Cohen EE, Needles BM, Cullen KJ, et al. Phase 2 study of sunitinib in refractory thyroid cancer. J Clin Oncol. 2008;26(15_suppl):Abstract 6025.

36. Carr LL, Mankoff DA, Goulart BH, et al. 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;16;5260-5266.

37. Sherman SI. Advances in chemotherapy of differentiated epithelial and medullary thyroid cancers. J Clin Endocrinol Metab. 2009;94:1493-1499.

38. Sunitinib (Sutent) [package insert]. New York, NY: Pfizer Labs; 2019.

39. Leboulleux S, Bastholt L, Krause T, et al. Vandetanib in locally advanced or metastatic differentiated thyroid cancer: A randomised, double-blind, phase 2 trial. Lancet Oncol. 2012;13:897-905.

40. Vandetanib (Caprelsa) [package insert]. Cambridge, MA: Genzyme Corp; 2018.

41. Vemurafenib (Zelboraf) [package insert]. South San Francisco, CA: Genentech, Inc.; 2017.

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(Revised 12/2020; NCCN Thyroid Carcinoma Guidelines v2.2020) © 2020 by Haymarket Media, Inc.