Tumor marker and measurement fluctuations may not reflect treatment efficacy in patients with medullary thyroid carcinoma on long-term RET inhibitor therapy.
BACKGROUND
RET kinase inhibitors have significant activity in patients with medullary thyroid carcinoma (MTC).


PATIENTS AND METHODS
We retrospectively reviewed the electronic medical record for patterns of calcitonin, carcinoembryonic antigen (CEA) and tumor measurement responses in consecutive patients with MTC who received treatment with a RET inhibitor for at least 6 months.


RESULTS
Twenty-six patients who received RET kinase inhibitors for at least 6 months were included. All patients experienced an initial decline in calcitonin; 20 (77%) demonstrated later fluctuations in calcitonin, which spiked above baseline levels in 9 individuals (35%). Twenty of the 22 patients (91%) with elevated CEA experienced a decline with treatment, with 11 individuals (50%) later demonstrating transient fluctuations in CEA, including spikes above baseline in 7 patients (32%). Ten of the 26 patients (38%) also demonstrated short-lived fluctuations in RECIST measurements, including changes of over 20% from nadir values. Vacillations in calcitonin, CEA and measurements often occurred repeatedly in individual patients and did not regularly correlate with each other.


CONCLUSIONS
Repeated transient fluctuations in tumor markers and measurements are a characteristic of patients with MTC receiving treatment with RET inhibitors, and such short-term vacillations may not reflect responsiveness over the long term.


CLINICAL TRIALS INCLUDED
NCT00215605; NCT00244972; NCT00121680; NCT00495872.