Does Cabozantinib (generic name: cabozantinib) affect thyroid profile?

Cabozantinib's Effects on Thyroid Profile

Cabozantinib can significantly affect thyroid function, commonly causing thyroid dysfunction with a predominant pattern of hypothyroidism, and in some cases causing a biphasic pattern of transient thyrotoxicosis followed by hypothyroidism. 1

Mechanisms and Patterns of Thyroid Dysfunction

• Cabozantinib is a tyrosine kinase inhibitor (TKI) that targets multiple pathways including VEGFR, MET, and RET, which are implicated in thyroid cancer pathogenesis 2
• Thyroid dysfunction is a common adverse event associated with cabozantinib treatment, affecting up to 93.1% of patients in clinical studies 1
• The most common pattern observed is subclinical hypothyroidism, though some patients develop clinically significant thyroid dysfunction requiring intervention 1
• A biphasic pattern characterized by transient thyrotoxicosis followed by hypothyroidism has been documented in some patients, with increased thyroid vascularization during the thyrotoxic phase 1

Clinical Presentation and Monitoring

• Thyroid dysfunction can manifest at various timepoints during treatment and requires regular monitoring 1
• Grade 3 or 4 treatment-related adverse events occurred in 57% of patients receiving cabozantinib in the COSMIC-311 trial, though specific thyroid dysfunction rates weren't highlighted in this guideline 3
• Early detection and characterization of cabozantinib-associated thyroid dysfunction is essential for proper management 1
• Patients may present with symptoms ranging from subclinical laboratory abnormalities to symptomatic thyrotoxicosis or hypothyroidism 1

Formulation and Dosing Considerations

• Cabozantinib is available in two formulations: tablets (60 mg daily) for differentiated thyroid cancer (DTC) and capsules (140 mg daily) for medullary thyroid cancer (MTC) 3
• These formulations are not bioequivalent and should not be used interchangeably 3
• Higher doses of cabozantinib (140 mg/day capsules) are associated with increased adverse events compared to lower doses (60 mg/day tablets), including potentially more thyroid-related effects 4
• Dose reductions are commonly required to manage adverse events, with 56% of patients in the COSMIC-311 trial requiring initial dose reduction and 22% requiring a secondary dose reduction 3

Management Recommendations

• Regular thyroid function monitoring should be performed in all patients receiving cabozantinib 1
• Close follow-up is essential to provide adequate management of this common adverse event 1
• Patients who develop symptomatic thyroid dysfunction may require appropriate thyroid hormone replacement therapy or other interventions based on the specific pattern of dysfunction 1
• Early detection and management of thyroid dysfunction is important to maintain quality of life and optimize treatment outcomes 1

Clinical Implications

• Thyroid dysfunction does not necessarily warrant discontinuation of cabozantinib therapy, as it can often be managed with appropriate interventions 1
• Only 5% of patients in the COSMIC-311 trial discontinued treatment due to treatment-related adverse events in general 3
• Understanding the potential for thyroid dysfunction is important when considering cabozantinib as a therapeutic option, particularly in the second-line setting after progression on other MKIs 3
• The risk-benefit profile should be considered in the context of cabozantinib's demonstrated efficacy in improving progression-free survival in patients with radioiodine-refractory DTC 3