What is the monitoring plan for a patient with medullary thyroid carcinoma (MTC) on Gavreto (pralsetinib)?

Monitoring Plan for Patients with Medullary Thyroid Carcinoma on Gavreto (Pralsetinib)

For patients with MTC on Gavreto, monitor serum calcitonin and CEA levels every 6 months during the first 2-3 years, then annually, with imaging frequency determined by tumor marker levels and doubling times. 1

Baseline Assessment Before Starting Gavreto

Before initiating pralsetinib therapy, establish baseline measurements that will guide all subsequent monitoring:

• Obtain serum calcitonin and CEA levels to establish tumor marker baseline status 2, 1
• Perform comprehensive imaging including contrast-enhanced CT of neck, chest, and abdomen; three-phase contrast-enhanced liver CT or MRI; bone scintigraphy; and MRI of spine/pelvis to document extent of metastatic disease 1, 3
• Calculate baseline calcitonin and CEA doubling times from sequential measurements if available, as these quantify disease aggressiveness and predict which patients require immediate intervention 1, 3

Tumor Marker Monitoring Schedule

The monitoring intensity depends on the calcitonin level and disease burden:

• Measure serum calcitonin every 6 months for the first 2-3 years, then annually thereafter 1
• Measure CEA concurrently with calcitonin, as rapidly increasing CEA with stable calcitonin predicts worse prognosis 3
• Recalculate doubling times from sequential measurements at each visit, as doubling time <6 months indicates aggressive disease requiring potential treatment modification 1

Important caveat: Calcitonin levels may decrease dramatically after RET inhibitor therapy without directly correlating with tumor volume changes, so calcitonin alone may not be a reliable marker of tumor response during active treatment 4. This makes imaging correlation essential.

Imaging Surveillance Strategy

Imaging frequency is stratified by calcitonin levels and clinical progression:

For Calcitonin <150 pg/mL:

• Perform cervical ultrasound every 6-12 months, as disease at this level is nearly always confined to cervical lymph nodes 1, 5
• No additional imaging required unless clinical symptoms develop 1

For Calcitonin ≥150 pg/mL:

• Perform contrast-enhanced CT of neck, chest, and abdomen to evaluate for distant metastases 2, 1
• Add hepatic triphasic CT or contrast-enhanced MRI for liver evaluation 1, 3
• Include bone scintigraphy and MRI of spine/pelvis for skeletal metastases 1, 3
• Consider FDG-PET/CT if calcitonin >1,000 pg/mL or doubling time <12 months 2

For Progressive Disease on Imaging:

• Use RECIST criteria to quantify tumor size changes over time from sequential imaging studies 5
• Imaging frequency should increase to every 2-3 months if rapid progression is suspected based on marker doubling times 4

Thyroid Function Monitoring

Maintain TSH in the normal range with levothyroxine replacement therapy only 2, 1. Unlike differentiated thyroid cancer, TSH suppression provides no benefit in MTC because C cells lack TSH receptors, and suppression increases risks of atrial fibrillation, osteoporosis, and cardiovascular complications 1, 3.

• Check TSH levels every 6-12 months to ensure adequate replacement without over-suppression 4

Clinical Assessment

At each follow-up visit:

• Perform physical examination focusing on cervical lymph nodes, signs of hormonal excess (diarrhea from calcitonin hypersecretion), and symptoms of metastatic disease 5
• Assess for symptomatic metastases requiring palliative intervention, including bone pain, bronchial obstruction, or spinal cord compression 5
• Monitor for Gavreto-related adverse effects as this will impact treatment continuation 6, 7

Critical Monitoring Pitfalls to Avoid

• Do not rely solely on calcitonin levels during RET inhibitor therapy, as they may not correlate with actual tumor response 4
• Do not delay comprehensive imaging when calcitonin exceeds 150 pg/mL or shows rapid doubling time, as this determines the entire treatment paradigm 3
• Do not attempt TSH suppression, as this provides no benefit and causes harm in MTC patients 1, 3
• Do not use radioiodine therapy or conventional cytotoxic chemotherapy, as MTC does not respond to these modalities 2, 3

When to Intensify Monitoring

Increase monitoring frequency to every 2-3 months if:

• Calcitonin or CEA doubling time <6 months 1
• Imaging shows progressive disease by RECIST criteria 5
• New symptoms develop suggesting metastatic progression 5
• Calcitonin >1,000 pg/mL regardless of imaging findings 2