Standard treatment options for iodine-resistant thyroid cancer

👉Standard treatment options for iodine-resistant thyroid cancer include the following:

1. Thyroid-suppression therapy.
2. Targeted therapy.
3. Surgery.
4. External-beam radiation therapy (EBRT).

👉Thyroid-suppression therapy

TSH suppression with thyroxine is effective in many lesions that are not sensitive to 131I

👉Targeted therapy

Sorafenib

Sorafenib is an orally active, multityrosine kinase inhibitor. 

Evidence (sorafenib):

• A phase III randomized, double-blind, placebo-controlled study (DECISION[NCT00984282]) evaluated the activity of sorafenib in patients with progressive, iodine-refractory differentiated thyroid cancer.
  • In the trial, 417 patients with locally advanced or metastatic RAI−refractory thyroid cancer (papillary, follicular [including Hürthle cell], and poorly differentiated, not anaplastic tumors, defined as beyond well-differentiated tumors or those well-differentiated tumors that become resistant to radioiodine treatment) whose disease had progressed within the past 14 months were randomly assigned to receive sorafenib (400 mg twice a day) or placebo.
  • Patients who received previous chemotherapy, thalidomide, or targeted therapy were excluded.
  • The median PFS in the sorafenib group was 10.8 months versus 5.8 months in the placebo group (hazard ratio [HR] 0.59; 95% confidence interval [CI], 0.45–0.76, P < .0001).
  • OS was not significantly improved (HR, 0.80; 95% CI, 0.54–1.19, P = .14, one-sided P-value), but the median OS had not been reached at the time of primary analysis data cutoff, and crossover was allowed.
  • Objective response rate (all partial responses) was 12.2% in the sorafenib group compared with 0.5% in the placebo group.
  • Median time-to-progression was 11.1 months in the sorafenib group compared with 5.7 months in the placebo group (HR, 0.56; 95% CI, 0.43–0.72, P < .001).
  • Adverse events occurred in 98.6% of patients treated with sorafenib and 87.6% of patients treated with placebo.
  • The most common adverse events in the sorafenib group were hand-foot skin reactions (76.3%), diarrhea (68.6%), alopecia (67.1%), and rash or desquamation (50.2%).
  • Most events were grade 1 or 2.
  • Seven squamous cell carcinomas of the skin occurred in the sorafenib group.

👉Lenvatinib

Lenvatinib is an orally active, multitargeted tyrosine kinase inhibitor.

Evidence (lenvatinib):

• A phase III, randomized, double-blind, placebo-controlled study (SELECT[NCT01321554]) evaluated the activity of lenvatinib in patients with progressive, iodine-refractory, differentiated thyroid cancer.
• In this trial, 261 patients were randomly assigned to receive lenvatinib (24 mg every day), and 131 patients were randomly assigned to receive placebo.
• Eligible patients had differentiated thyroid cancer (including papillary, follicular, poorly differentiated, and Hürthle cell carcinomas), RAI-refractory disease, and evidence of radiological progression within the previous 13 months.
• At disease progression, patients in the placebo group could receive open-label lenvatinib.
  • The primary endpoint was PFS, and secondary endpoints were OS, response rate, and safety.
  • The median PFS in the lenvatinib group was 18.3 months versus 3.6 months in the placebo group (HR_{progression or death}, 0.21; 99% CI, 0.14–0.31; P < .001).
  • A PFS difference was observed in patients with all histologic types of thyroid cancer enrolled in this trial.
  • There was no significant difference in OS between the two groups (HR _death, 0.73; 95% CI, 0.50–1.07; P = .10), even with the crossover design of the study.
  • Objective response rate was 64.8% in the lenvatinib group versus 1.5% in the placebo group (odds ratio [OR], 28.87; 95% CI, 12.46–66.86; P < .001).
  • Treatment-related adverse events (all grades) occurred in 97.3% of patients in the lenvatinib group and 59.5% of patients in the placebo group.
    • Grade 3 or higher adverse events were observed in 75.9% of patients receiving lenvatinib and 9.9% of patients receiving placebo.
    • The most common adverse events in the lenvatinib group were hypertension (67.8%), diarrhea (59.4%), fatigue (59%), decreased appetite (50.2%), decreased weight (46.4%), and nausea (41%).
    • Discontinuation of the study drug because of adverse events occurred in 14.2% of patients receiving lenvatinib and 2.3% of patients receiving placebo.
    • In the lenvatinib group, 6 of 20 deaths occurring during the treatment period were considered drug related.

👉Surgery

Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of 131I

👉EBRT

EBRT is considered for patients with localized lesions that are unresponsive to 131I

👉Treatment options under clinical evaluation for metastatic papillary and follicular thyroid cancer

👉Patients unresponsive to 131I should also be considered candidates for clinical trials testing new approaches to this disease.

• Chemotherapy has been reported to produce occasional complete responses of long duration.
• Clinical trials evaluating new treatment approaches to this disease should be considered for patients with radioiodine-refractory papillary or follicular thyroid cancer.
• Oral inhibitors targeting specific activating point mutations are under clinical evaluation, as are new immunotherapy approaches.

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