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.

▶Papillary Carcinoma1,b,c

REGIMEN

DOSING

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

Preferred Regimens

Lenvatinib (Category 1)2-5,d,e

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

Repeat cycle every 4 weeks.

Other Recommended Regimens

Sorafenib (Category 1)6-8,d,e

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

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Axitinib9-12,f

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

Repeat cycle every 4 weeks.

Cabozantinib (Category 1)
(if progression after Lenvatinib and/or Sorafenib)13-15

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Dabrafenib (for patients with BRAF V600-activating mutation)16-18,f

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

Repeat cycle every 4 weeks.

Dabrafenib/Trametinib (for patients with BRAF V600-activating mutation and progressive disease with prior treatment with no satisfactory alternative treatment options)16,18,19

Days 1-28: Dabrafenib 150mg twice daily

Days 1-28: Trametinib 2mg orally daily.

Repeat cycle every 4 weeks.

Entrectinib (for patients with NTRK gene fusion-positive tumors)20-22

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

Repeat cycle every 4 weeks.

Everolimus23-25,f

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

Repeat cycle every 4 weeks.

Larotrectinib (for patients with NTRK gene fusion-positive tumors)26,27

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

Repeat cycle every 4 weeks.

Pazopanib28,29,f

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

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g

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 6 weeks for up to 2 years.

Pralsetinib (for patients with RET fusion-positive tumors)33-35

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38

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.

Sunitinib39-41,f

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.

Vandetinib42,43,f,k

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

Repeat cycle every 4 weeks.

Vemurafenib (for patients with BRAF V600-activating mutation)44,45,f

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

Repeat cycle every 4 weeks

▶Follicular Carcinoma1,c,h

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

Preferred Regimens

Lenvatinib (Category 1)2-5,d,e

Days 1-28: Lenvatinib 24mg once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Sorafenib (Category 1)6-8,d,e

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

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Axitinib9-12,f

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

Repeat cycle every 4 weeks.

Cabozantinib (if progression after lenvatinib and/or sorafenib)13-15

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Dabrafenib (for patients with BRAF V600-activating mutation)16-18,f

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

Repeat cycle every 4 weeks.

Dabrafenib/Trametinib
(for patients with BRAF V600- activating mutation and progressive disease with prior treatment with no satisfactory alternative treatment options)16,18,19

Days 1-28: Dabrafenib 150mg twice daily

Days 1-28: Trametinib 2mg orally daily.

Repeat cycle every 4 weeks.

Entrectinib (for patients with NTRK gene fusion-positive tumors)20-22

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

Repeat cycle every 4 weeks.

Everolimus23-25,f

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

Repeat cycle every 4 weeks.

Larotrectinib (for patients with NTRK gene fusion-positive tumors)26,27

Days 1-28: Larotrectinib 100mg twice daily.

Repeat cycle every 4 weeks.

Pazopanib28,29,f

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

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g

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 6 weeks for up to 2 years.

Pralsetinib (for patients with RET fusion-positive tumors)33-35

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38

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.

Sunitinib39,40,46,f

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.

Vandetinib42,43,f,k

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

Repeat cycle every 4 weeks.

Vemurafenib (for patients with BRAF V600-activating mutation)44,45,f

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

Repeat cycle every 4 weeks.

▶Hürthle Cell Carcinoma1,c,i

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

Preferred Regimens

Lenvatinib (Category 1)2-5,d,e

Days 1-28: Lenvatinib 24mg once daily.

Repeat cycle every 4 weeks.

Other Recommended Regimens

Sorafenib (Category 1)6-8,d,e

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

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Axitinib9-11,f

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

Repeat cycle every 4 weeks.

Cabozantinib (if progression after lenvatinib and/or sorafenib)13-15

Days 1-28: Cabozantinib 60mg orally once daily.

Repeat cycle every 4 weeks.

Dabrafenib (for patients with BRAF V600-activating mutation)16-18,f

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

Repeat cycle every 4 weeks.

Dabrafenib/Trametinib (for patients with BRAF V600- activating mutation and progressive disease with prior treatment with no satisfactory alternative treatment options)16,18,19

Days 1-28: Dabrafenib 150mg twice daily

Days 1-28: Trametinib 2mg orally daily.

Repeat cycle every 4 weeks.

Entrectinib (for patients with NTRK gene fusion-positive tumors)20-22

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

Repeat cycle every 4 weeks.

Everolimus23-25,f

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

Repeat cycle every 4 weeks.

Larotrectinib (for patients with NTRK gene fusion-positive tumors)26,27

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

Repeat cycle every 4 weeks.

Pazopanib28,29,f

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

Repeat cycle every 4 weeks.

Pembrolizumab (for patients with TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g

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 6 weeks for up to 2 years.

Pralsetinib (for patients with RET fusion-positive tumors)33-35

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38

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.

Sunitinib39-41,f

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.

Vandetinib42,43,f,k

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

Repeat cycle every 4 weeks.

Vemurafenib (for patients with BRAF V600-activating mutation)44,45,f

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

Repeat cycle every 4 weeks.

▶Medullary Carcinoma1

Systemic Therapy For Treatment of Recurrent or Persistent Locoregional Diseased

Preferred Regimens

Cabozantinib (Category 1)13,47,48

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

Repeat cycle every 4 weeks.

Pralsetinib (for patients with RET fusion-positive tumors)33,35,j

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38,j

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.

Vandetinib (Category 1)42,49,f,k

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

Repeat cycle every 4 weeks.

Useful in Certain Circumstances

Pembrolizumab (for patients with TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g,j

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 6 weeks for up to 2 years.

Systemic Therapy For Treatment of Recurrent or Persistent Distant Metastases

Asymptomatic Diseased

Preferred Regimens

Cabozantinib (Category 1)13,47,48

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

Repeat cycle every 4 weeks.

Pralsetinib (for patients with RET fusion-positive tumors)33-35,j

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38,j

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.

Vandetinib (Category 1)42,49,f,k

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

Repeat cycle every 4 weeks

Useful in Certain Circumstances

Pembrolizumab (for patients with TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g,j

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 6 weeks for up to 2 years.

Symptomatic Disease or Progressiond

Preferred

Cabozantinib (Category 1)13,47,48

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

Repeat cycle every 4 weeks.

Pralsetinib (for patients with RET fusion-positive tumors)33-35,j

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38,j

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.

Vandetinib (Category 1)42,49,f,k

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

Repeat cycle every 4 weeks.

Other Recommended Regimens

Doxorubicin/Streptozocin Alternating With Fluorouracil/Dacarbazine50-54,m,n

Day 1: Doxorubicin 60mg/m2 IV push

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

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

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

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

Administer for one 4-week cycle (even cycle).

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

Fluorouracil/Dacarbazine Alternating With Fluorouracil/Streptozocin50,52,53,55,n

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

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

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

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

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

Administer for one 3-week cycle (even cycle).

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

Lenvatinib2,56,l

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

Repeat cycle every 4 weeks.

Pazopanib28,57,l

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

Repeat cycle every 4 weeks.

Sorafenib6,58,59,l

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

Repeat cycle every 4 weeks.

Sunitinib39-41,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 TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g,j

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 6 weeks for up to 2 years.

▶Anaplastic Carcinoma1

Adjuvant/Radiosensitizing Chemotherapy Regimens

Other Recommended Regimens

Docetaxel60-62

Docetaxel requires premedication.o

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

Repeat cycle weekly.

Docetaxel/Doxorubicin51,60,61,m

Docetaxel requires premedication.o

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

Day 1: Doxorubicin 20mg/m2 IV push.

Repeat cycle weekly for 6 weeks with concurrent radiation.

Paclitaxel61,63

Paclitaxel requires premedication.p

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

Repeat cycle weekly for 6 weeks with concurrent radiation.

Paclitaxel/Carboplatin61,63,64

Paclitaxel requires premedication.p

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 Regimens

Dabrafenib/Trametinb (for patients with BRAF V600- activating mutation)16,18,19,65

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)20-22,66

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

Repeat cycle every 4 weeks

Larotrectinib (for patients with NTRK gene fusion positive tumors)26,27,66

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

Repeat cycle every 4 weeks.

Pralsetinib (for patients with RET fusion-positive tumors)33-35

Days 1-28: Pralsetinib 400mg orally daily.

Repeat cycle every 4 weeks.

Selpercatinib (for patients with RET fusion-positive tumors)36-38,67

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.

Other Recommended Regimens

Docetaxel/Doxorubicin51,60,68,m,q

Docetaxel requires premedication.o

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

Day 1: Doxorubicin 60mg/m2 IV push.

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

OR

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

Day 1: Doxorubicin 20mg/m2 IV push.

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

Doxorubicin51,68,69,m

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.

Paclitaxel63,70

Paclitaxel requires premedication.p

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/Carboplatin64,68,70,71

Paclitaxel requires premedication.p

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

Doxorubicin/Cisplatin51,61,72,73m,r

Day 1: Cisplatin 40mg/m2 IV over 60 minutes

Day 1: Doxoruicin 60mg/m2 IV push.

Repeat cycle every 3 weeks.

Pembrolizumab (for patients with TMB-H (defined as tumors with ≥10 mut/Mb)30-32,g,j

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 6 weeks for up to 2 years.

  a RAI, radioactive iodine; TMB-H, tumor mutational burden-high; mut/MB, mutations/megabase.

b 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.

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

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

e Tyrosine kinase inhibitor (TKI) therapy should be used with caution in otherwise untreated CNS metastases due to bleeding risk.

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

g Early- and late-onset immune-related adverse events affecting multiple organ systems can occur in patients receiving immune checkpoint inhibitors. Patients with neurologic or life-threatening autoimmune disorders as well as receiving high levels of immunosuppression for their underlying disease should be approached with caution when considering immunotherapy. All patients will require extensive resources including ongoing intensive monitoring and supportive care.

h 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.

i 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.

j Genomic testing including TMB or RET somatic genotyping in patients who are germline wild-type or germline unknown.

k 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.

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 or preferred systemic therapy options are not available or appropriate, or if the patient progresses on preferred systemic therapy options.

m Doxorubicin is an anthracycline. Cumulative anthracycline dosage should be monitored.

n Patients with dihydropyrimidine dehydrogenase (DPD) deficiency are unable to metabolize this agent normally and may have severe unexpected toxicity. Review drug package insert for clinical pharmacology, precautions, warnings, and recommendations.

o For Docetaxel: Premedication with Dexamethasone for fluid retention is required. One recommended strategy is:

  i. Dexamethasone 8mg orally twice daily for three consecutive days starting 1 day prior to Docetaxel administration.

p For Paclitaxel: Premedication for hypersensitivity is required. The recommended dosing is:

  i. H2 antagonist

    1. Famotidine 20mg IV or orally (or equivalent H2 blocker) 30-60 minutes pre-Paclitaxel AND

  ii. H1 antagonist

    1. Diphenhydramine 12.5-50mg IV or orally 30-60 minutes pre-Paclitaxel AND

  iii. Dexamethasone (for 21-day regimen):

    1. Dexamethasone 20mg orally approximately 12 and 6 hours pre-Paclitaxel OR

    2. Dexamethasone 20mg IV 30 minutes pre-Paclitaxel OR

  iv. Dexamethasone (for weekly regimens):

    1. Dexamethasone 10mg IV 30 minutes pre-Paclitaxel.

  v. In the absence of infusion reactions for Doses 1-3, may consider Dexamethasone 4mg IV 30 minutes pre-Paclitaxel starting with Dose 4.

q Myeloid growth factor therapy recommended.

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

References

  1. Referenced with permission from NCCN Clinical Practice Guidelines in Oncology™. Thyroid Carcinoma. V.3.2022. Available at: https://www.nccn.org/professionals/physician_gls/pdf/thyroid.pdf. Accessed November 30, 2022.

  2. Levantinib (Lenvima) [package insert]. Nutley, NJ: Eisai Inc.; November 2022. https://www.lenvima.com/-/media/Project/EIsai/
Lenvima/PDF/prescribing-information.pdf?hash=8e823de7-4207-411d-8b00-48ac4ea27356&v=2020-12-22. Accessed December 2, 2022.

  3. Brose MS, Worden FP, Newbold KL, Guo M, Hurria A. 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(23):2692-2699. doi: 10.1200/JCO.2016.71.6472.

  4. 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(16): 2749-2756. doi: 10.1002/cncr.29395.

  5. Schlumberger M, Tahara M, Wirth LJ, et al. Lenvatinib versus placebo in radioiodine-refractory thyroid cancer. N Engl J Med. 2015;372(7):621-630.

  6. Sorafenib (Nexavar) [package insert]. Whippany, NJ: Bayer Healthcare Pharmaceuticals Inc. July 2020. https://labeling.bayerhealthcare.com/html/products/pi/Nexavar_PI.pdf. Accessed December 2022.

  7. 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(9940):319-328. doi: 10.1016/S0140-6736(14)60421-9.

  8. Kloos RT, Ringel MD, Knopp MV, et al. Phase II trial of sorafenib in metastatic thyroid cancer. J Clin Oncol. 2009;27(10):1675-1684. doi: 10.1200/JCO.2008.18.2717.

  9. Axitinib (Inlyta) [package insert]. New York, NY: Pfizer Inc. September 2022. https://labeling.pfizer.com/ShowLabeling.aspx?id=759. Accessed December 2022.

10. Cohen EE, 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(29):4708-4713. doi: 10.1200/JCO.2007.15.9566.

11. Cohen EE, Tortorici M, Kim S, Ingrosso A, Pithavala YK, Bycott P. A Phase II trial of axitinib in patients with various histologic subtypes of advanced thyroid cancer: long-term outcomes and pharmacokinetic/pharmacodynamic analyses. Cancer Chemother Pharmacol. 2014;74(6):1261-1270. doi: 10.1007/s00280-014-2604-8.

12. 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(17):2694-2703. doi: 10.1002/cncr.28766.

13. Cabozantinib (Cabometyx) [package insert]. Alemeda, CA: Exelixis, Inc.; July 2022. Exelixis_NDA 208692 Approval and Label_Emailed.pdf (cabometyxhcp.com). Accessed December 2, 2022.

14. Brose MS, Robinson B, Sherman SI, et al. Cabozantinib for radioiodine-refractory differentiated thyroid cancer (COSMIC-311): a randomised, double-blind, placebo- controlled, phase 3 trial. Lancet Oncol. 2021;22(8):1126-1138. doi: 10.1016/S1470-2045(21)00332-6.

15. Cabinillas 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(29):3315-3312. doi: 10.1200/JCO.2017.73.0226.

16. Dabrafenib (Tafinlar) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; June 2022. TAFINLAR capsules (novartis.com). Accessed December 2, 2022.

17. Falchook GS, Millward M, Hong D, et al. BRAF inhibitor dabrafenib in patients with metastatic BRAF-mutant thyroid cancer. Thyroid. 2015;25(1):71-77. doi: 10.1089/thy.2014.0123.

18. Subbiah 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(1):7-13. doi: 10.1200/JCO.2017.73.6785.

19. Trametinib (Mekinist) [package insert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; June 2022. mekinist tablets (novartis.com). Accessed December 2, 2022.

20. Entrectinib (Rozlytrek) [package insert]. South San Francisco, CA: Genentech USA, Inc.; July 2022. rozlytrek_prescribing.pdf (gene.com). Accessed December 2, 2022.

21. Doebele RC, Drilon A, Paz-Ares L, et al. Entrectinib in patients with advanced or metastatic NTRK fusion-positive solid tumours: integrated analysis of three phase 1-2 trials. Lancet Oncol. 2020;21(2):271-282. doi: 10.1016/S1470-2045(19)30691-6.

22. Drilon A, Siena S, Ou SI, 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(4):400-409. doi: 10.1158/2159-8290.CD-16-1237.

23. Everolimus (Afinitor) [package insert]. ]. East Hanover, NJ: Novartis Pharmaceuticals Corporation; February 2022. afinitor (novartis.com). Accessed December 2, 2022.

24. 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(12):3089-3094. doi: 10.1093/annonc/mdt379.

25. 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 [published correction appears in J Clin Endocrinol Metab. 2017 Jun 1;102(6):2125]. J Clin Endocrinol Metab. 2017;102(2):698-707. doi: 10.1210/jc.2016-2525.

26. Larotrectinib (Vitrakvi) [package insert]. Whippany, NJ: Bayer Healthcare Corporation; November 2022. vitrakvi_PI.pdf (bayerhealthcare.com). Accessed December 2, 2022.

27. 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(8):731-739. doi: 10.1056/NEJMoa1714448.

28. Pazopanib (Votrient) [package insert]. East Hanover, NJ. Novartis Pharmaceuticals Corporation; December 2021. votrient tablets (novartis.com). Accessed December 2, 2022.

29. 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(10):962-972. doi: 10.1016/S1470-2045(10)70203-5.

30. Pembrolizumab (Keytruda) [package insert]. Whitehouse Station, NJ: Merck & Co. Inc.; August 2022. keytruda_pi.pdf (merck.com). Accessed December 2, 2022.

31. Lala M, Li TR, de Alwis DP, et al. A six-weekly dosing schedule for pembrolizumab in patients with cancer based on evaluation using modelling and simulation [published correction appears in Eur J Cancer. 2021 Feb;144:400]. Eur J Cancer. 2020;131:68-75. doi: 10.1016/j.ejca.2020.02.016.

32. Marabelle A, Fakih M, Lopez J, et al. Association of tumour mutational burden with outcomes in patients with advanced solid tumours treated with pembrolizumab: prospective biomarker analysis of the multicohort, open-label, phase 2 KEYNOTE-158 study. Lancet Oncol. 2020;21(10):1353-1365. doi: 10.1016/S1470-2045(20)30445-9.

33. Pralsetinib (Gavreto) [package insert]. South San Francisco, CA: Genentech Inc.; September 2022. gavreto_prescribing.pdf (gene.com). Accessed December 2, 2022.

34. Subbiah V, Hu M, Gainor J, et al. Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion+ solid tumors [abstract]. J Clin Oncol. 2020;38 (suppl_15):Abstract 109.

35. Subbiah V, Hu MI-C, Gainor JF, et al. Clinical activity of the RET inhibitor pralsetinib (BLU-667) in patients with RET fusion-positive solid tumors [abstract]. J Clin Oncol. 2021;39(3_suppl): Abstract 467.

36. Selpercatinib (Retevmo) [package insert]. Indianapolis, IN: Lilly USA, LLC; September 2022. https://uspl.lilly.com/retevmo/retevmo.html#pi. Accessed December 2, 2022.

37. Shah M, Sherman E, Robinson B, et al. Selpercatinib (LOXO-292) in patients with RET-mutant medullary thyroid cancer [abstract]. J Clin Oncol. 2020;38 (suppl_15):Abstract 3594.

38. Wirth L, Sherman E, Drilon A, et al. LBA93 – Registrational results of LOXO-292 in patients with RET-altered thyroid cancers [abstract]. Ann Oncol. 2019;30(5):v933.

39. Sunitinib (Sutent) [package insert]. New York, NY: Pfizer Inc.; August 2021. https://labeling.pfizer.com/ShowLabeling.aspx?id=607. Accessed December 2, 2022.

40. 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(21):5260-5268. doi: 10.1158/1078-0432.CCR-10-0994.

41. Cohen EE, Needles BM, Cullen KJ, et al. Phase 2 study of sunitinib in refractory thyroid cancer [abstract]. J Clin Oncol. 2008;26(suppl_15):Abstract 6035.

42. Vandetinib (Caprelsa) [package insert]. Cambridge, MA: Genzyme Corporation; March 2022. caprelsa.pdf (sanofi.us). Accessed December 2, 2022.

43. 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(9):897-905. doi: 10.1016/S1470-2045(12)70335-2.

44. Vemurafenib (Zelboraf) [package insert]. South San Francisco: Genentech, Inc.; May 2020. https://www.gene.com/download/pdf/zelboraf_prescribing.pdf. Accessed December 2, 2022.

45. Brose MS, Cabanillas ME, Cohen EE, et al. Vemurafenib in patients with BRAF(V600E)-positive metastatic or unresectable papillary thyroid cancer refractory to radioactive iodine: a non-randomised, multicentre, open-label, phase 2 trial. Lancet Oncol. 2016;17(9):1272-1282. doi: 10.1016/S1470-2045(16)30166-8.

46. Cabanillas ME, Waguespack SG, Bronstein Y, et al. Treatment with tyrosine kinase inhibitors for patients with differentiated thyroid cancer: the M. D. Anderson experience. J Clin Endocrinol Metab. 2010;95(6):2588-2595. doi: 10.1210/jc.2009-1923.

47. Elisei R, Schlumberger MJ, Müller SP, et al. Cabozantinib in progressive medullary thyroid cancer [published correction appears in J Clin Oncol. 2014 Jun 10;32(17):1864]. J Clin Oncol. 2013;31(29):3639-3646. doi: 10.1200/JCO.2012.48.4659.

48. Schlumberger M, Elisei R, Müller S, et al. Overall survival analysis of EXAM, a phase III trial of cabozantinib in patients with radiographically progressive medullary thyroid carcinoma. Ann Oncol. 2017;28(11):2813-2819. doi: 10.1093/annonc/mdx479.

49. Wells SA Jr, Robinson BG, Gagel RF, et al. Vandetanib in patients with locally advanced or metastatic medullary thyroid cancer: a randomized, double-blind phase III trial [published correction appears in J Clin Oncol. 2013 Aug 20;31(24):3049]. J Clin Oncol. 2012;30(2):134-141. doi: 10.1200/JCO.2011.35.5040.

50. Dacarbazine [package insert]. Parsippany, NJ: Teva Parenteral Medicines, Inc.; February 2020. Dacarbazine for Injection, USP (nih.gov). Accessed December 2, 2022.

51. Doxorubicin [package insert]. Lake Zurich, IL: Fresenius Kabi; August 2016. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=e0349f98-42fa-4003-b6d8-a1db1401b0ef&type=display. Accessed December 2, 2022.

52. Fluorouracil [package insert]. ]. Lake Zurich, IL: Fresenius Kabi; April 2017. https://dailymed.nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=fdf2a165-2ca4-48be-89c1- 570e6010b47c&type=display. Accessed December 2, 2022.

53. Streptozocin [package insert]. Parsippany, NJ: Teva Parenteral Medicines, Inc.; January 2022. ZANOSAR® (Streptozocin Sterile Powder) (nih.gov). Accessed December 2, 2022.

54. Nocera M, Baudin E, Pellegriti G, Cailleux AF, Mechelany-Corone C, Schlumberger M. Treatment of advanced medullary thyroid cancer with an alternating combination of doxorubicin-streptozocin and 5 FU-dacarbazine. Groupe d’Etude des Tumeurs à Calcitonine (GETC). Br J Cancer. 2000;83(6):715-718. doi: 10.1054/bjoc.2000.1314.

55. Schlumberger M, Abdelmoumene N, Delisle MJ, Couette JE. Treatment of advanced medullary thyroid cancer with an alternating combination of 5 FU-streptozocin and 5 FU-dacarbazine. The Groupe d’Etude des Tumeurs a Calcitonine (GETC). Br J Cancer. 1995;71(2):363-365. doi: 10.1038/bjc.1995.73.

56. Schlumberger M, Jarzab B, Cabanillas ME, et al. A phase II trial of the multitargeted tyrosine kinase inhibitor lenvatinib (E7080) in advanced medullary thyroid cancer. Clin Cancer Res. 2016;22(1):44-53. doi: 10.1158/1078-0432.CCR-15-1127.

57. Bible KC, Suman VJ, Molina JR, et al. A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H. J Clin Endocrinol Metab. 2014;99(5):1687-1693. doi: 10.1210/jc.2013-3713.

58. Gupta-Abramson V, Troxel AB, Nellore A, et al. Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol. 2008;26(29):4714-4719.

59. Lam ET, Ringel MD, Kloos RT, et al. Phase II clinical trial of sorafenib in metastatic medullary thyroid cancer. J Clin Oncol. 2010;28(14):2323-2330. doi: 10.1200/JCO.2009.25.0068.

60. Docetaxel [package insert]. Lake Forest, IL: Hospira, Inc.; June 2021. https://dailymed. nlm.nih.gov/dailymed/fda/fdaDrugXsl.cfm?setid=a0ec4bcc-93ea-4c41-a4b6- 95ec19491807&type=display. Accessed December 2, 2022.

61. Bible KC, Kebebew E, Brierley J, et al. 2021 American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2021;31:337-386. doi: 10.1089/thy.2020.0944.

62. Troch M, Koperek O, Scheuba C, et al. High efficacy of concomitant treatment of undifferentiated (anaplastic) thyroid cancer with radiation and docetaxel. J Clin Endocrinol Metab. 2010;95(9):E54-E57. doi: 10.1210/jc.2009-2827

63. Paclitaxel [package insert]. North Wales, PA: Teva Pharmaceuticals USA, Inc.; July 2015. Paclitaxel Injection USP (nih.gov). Accessed December 2, 2022.

64. Carboplatin [package insert]. Lake Zurich, IL: Fresenius Kabi; May 2021. CARBOplatin Injection (nih.gov). Accessed December 2, 2022.

65. DeBois SG, Laetsch TW, Federman N, et al. The use of neoadjuvant larotrectinib in the management of children with locally advanced TRK fusion sarcomas. Cancer. 2018;124(21):4241-4247. doi: 10.1002/cncr.31701.

66. Cabanillas ME, Ferrarotto R, Garden AS, et al. Neoadjuvant BRAF- and immune-directed therapy for anaplastic thyroid carcinoma. Thyroid. 2018;28(7):945-951. doi: 10.1089/thy.2018.0060

67. Jozaghi Y, Zafereo M, Williams MD, et al. Neoadjuvant selpercatinib for advanced medullary thyroid cancer. Head Neck. 2021;43(1):E7-E12. doi: 10.1002/hed.26527.

68. Smallridge RC, Ain KB, Asa SL, et al. American Thyroid Association guidelines for management of patients with anaplastic thyroid cancer. Thyroid. 2012;22(11): 1104-1139. doi: 10.1089/thy.2012.0302.

69. Swaak-Kragten AT, de Wilt JH, Schmitz PI, Bontenbal M, Levendag PC. Multimodality treatment for anaplastic thyroid carcinoma–treatment outcome in 75 patients. Radiother Oncol. 2009;92(1):100-104. doi: 10.1016/j.radonc.2009.02.016.

70. Higashiyama T, Ito Y, Hirokawa M, et al. Induction chemotherapy with weekly paclitaxel administration for anaplastic thyroid carcinoma. Thyroid. 2010;20(1): 7-14. doi: 10.1089/thy.2009.0115.

71. Sosa JA, Elisei R, Jarzab B, et al. Randomized safety and efficacy study of fosbretabulin with paclitaxel/carboplatin against anaplastic thyroid carcinoma. Thyroid. 2014;24(2):232-240. doi: 10.1089/thy.2013.0078.

72. Cisplatin [package insert]. March 2017. Lake Zurich, IL: Fresenius Kabi; Cisplatin Injection (nih.gov). Accessed December 2, 2022.

73. Shimaoka K, Schoenfeld DA, DeWys WD, Creech RH, DeConti R. A randomized trial of doxorubicin versus doxorubicin plus cisplatin in patients with advanced thyroid carcinoma. Cancer. 1985;56(9):2155-2160. doi: 10.1002/1097-0142 (19851101)56:9<2155::aid-cncr2820560903>3.0.co;2-e.

(Revised 2/2023; NCCN Thyroid Carcinoma Guidelines v3.2022) © 2023 by Haymarket Media, Inc.

Topics:

Endocrine Cancer Thyroid Cancer Treatment Regimens