👉Standard treatment options for iodine-resistant thyroid cancer include the following:
TSH suppression with thyroxine is effective in many lesions that are not sensitive to 131I
Sorafenib is an orally active, multityrosine kinase inhibitor.
- 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 is an orally active, multitargeted tyrosine kinase inhibitor.
- 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 (HRprogression 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.
Resection of limited metastases, especially symptomatic metastases, should be considered when the tumor has no uptake of 131I
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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