A team of German researchers, noting the lack of research on the discontinuation of tyrosine kinase inhibitors (TKIs) after long-term therapy in patients with medullary thyroid carcinoma (MTC), discovered that the discontinuation of vandetanib in patients with stable disease did not automatically cause rapid disease progression. Instead, a period of prolonged “TKI-free” stable disease was observed in some patients, according to a study published in Frontiers in Endocrinology.
In Germany, 2 TKIs are approved for use in patients with MTC: vandetanib and cabozantinib. It is important to note that even patients with advanced MTC can be free of symptoms and remain stable for a long period. The indication for use of TKIs in patients with MTC is aggressive and symptomatic MTC with unresectable locally advanced or metastatic disease.
Read more about MTC etiology
Recently, attention has turned toward the safety profile of the long-term use of these TKIs. Some patients are unable to tolerate long-term use of TKIs due to adverse effects; others outright refuse to continue treatment. “In these situations,” the authors of the study wrote, “little is known about the natural course of the disease.” The authors hence set out to investigate the effects of vandetanib discontinuation after long-term usage.
The researchers recruited patients with MTC who were seen at the Endocrine Tumor Center at the University of Duisburg-Essen in Germany. The inclusion criterion was the discontinuation of vandetanib after a period of long-term usage. Out of 161 patients, 7 patients fit the inclusion criteria.
Each of the 7 patients had a unique treatment trajectory. Two of them (29%) who were on vandetanib—one for 73 months and one for 58 months—remained stable after discontinuation until follow-up at 47 and 61 months. The other 5 patients (71%) developed progressive disease following TKI discontinuation. Of these 5 patients, 2 resumed treatment after 45 and 52 months, respectively, which restored disease control; 1 patient enrolled in a RET kinase inhibitor trial 45 months after discontinuation, and 2 declined the restart of vandetanib due to mental health reasons and died of rapidly progressive disease.
This study demonstrates 2 things. First, TKI treatment that has been initiated should be continued in most circumstances due to the clear clinical benefits. Second, treatment cessation does not automatically trigger rapid disease progression.
Other studies suggest that the far more important factor for survival is how early TKI treatment is initiated. Valerio et al conducted a study on the use of vandetanib in younger patients and commented, “Early treatment with vandetanib, when patients are younger… [seems] to be the best [predictor] of a longer and durable response.”
Brandenburg T, Tiedje V, Muchalla P, et al. Continued discontinuation of TKI treatment in medullary thyroid carcinoma – lessons from individual cases with long-term follow-up. Front Endocrinol. Published online September 29, 2021. doi:10.3389/fendo.2021.718418
Valerio L, Bottici V, Matrone A, et al. Medullary thyroid cancer treated with vandetanib: predictors of a longer and durable response. Endocr Relat Cancer. 2020;27(2):97-110. doi:10.1530/ERC-19-0259