From the Guidelines
Radioiodine-refractory differentiated thyroid cancer (DTC) should be identified and treated with targeted systemic therapies, such as lenvatinib or sorafenib, as first-line treatment, as they have demonstrated improved progression-free survival, as shown in the ESMO clinical practice guideline update on the use of systemic therapy in advanced thyroid cancer 1. The identification of RAI-R DTC is crucial, as it directly informs prognosis, surveillance strategies, and therapeutic decisions. Specific clinical criteria for identification include lack of radioiodine uptake in all lesions, tumor progression despite radioiodine treatment, persistent disease after cumulative doses exceeding 600 mCi, or FDG-avid lesions without corresponding radioiodine uptake. Some key points to consider in the management of RAI-R DTC include:
- Treatment should be initiated when there is documented progressive disease or symptomatic metastases, as asymptomatic stable disease may be monitored without immediate intervention, as suggested by the NCCN guidelines insights: thyroid carcinoma, version 2.2018 1.
- Surveillance should include more frequent imaging (every 3-6 months) with CT or MRI, and measurement of thyroglobulin levels, as recommended by the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of thyroid cancer 1.
- Dose modifications of TKIs are often necessary to manage side effects while maintaining therapeutic efficacy, as noted in the ESMO clinical practice guideline update on the use of systemic therapy in advanced thyroid cancer 1. The shift to RAI-refractoriness represents dedifferentiation of thyroid cancer cells with loss of sodium-iodide symporter function, explaining why conventional radioiodine therapy becomes ineffective and why more aggressive treatment approaches are required. Some of the treatment options for RAI-R DTC include:
- Lenvatinib, which has demonstrated a progression-free survival gain of 14.7 months, as shown in the SELECT trial 1.
- Sorafenib, which has demonstrated a progression-free survival gain of 5.0 months, as shown in the DECISION trial 1.
- Cabozantinib, which has demonstrated a progression-free survival gain of 6.7 months, as shown in the COSMIC-311 trial 1.
From the Research
Accurate Identification of RAI Refractoriness
Accurate identification of RAI refractoriness is crucial in determining prognosis, surveillance strategies, and therapeutic decisions for patients with differentiated thyroid cancer (DTC) 2, 3, 4, 5, 6.
Treatment Options for RAI-Refractory DTC
Several treatment options are available for RAI-refractory DTC, including:
- Targeted multikinase inhibitors such as sorafenib and lenvatinib 2, 3, 4, 5, 6
- Tyrosine kinase inhibitors (TKIs) such as axitinib, motesanib, pazopanib, sunitinib, and vandetinib 3
- BRAF inhibitors for patients with BRAF V600E mutation 4
- Other TKIs such as apatinib and anlotinib 6
Key Considerations for Treatment
Key considerations for treatment of RAI-refractory DTC include:
- Tumor size and growth rate 2
- Patient and disease characteristics 4, 5
- Side effect profile and management 2, 3, 4, 5, 6
- Financial toxicity 5
Efficacy of TKIs
TKIs have shown efficacy in improving progression-free survival (PFS) and overall survival (OS) in patients with RAI-refractory DTC 3, 4, 5, 6.
- Lenvatinib has demonstrated the greatest benefit in terms of PFS 6
- Apatinib and anlotinib have shown statistically significant benefits in terms of OS compared with placebo 6
Adverse Events
TKIs are associated with a spectrum of adverse events, including dermatologic, gastrointestinal, and cardiovascular toxicities 3, 4, 5, 6.
- Lenvatinib has a high incidence of adverse events of grade 3 or higher 6