Variants in the RET gene are prevalent among patients with advanced medullary thyroid carcinoma (MTC), according to a study published in Cancers.

The results of treatment with multityrosine kinase inhibitors in patients who are RET positive are similar to those in unselected cohorts. This supports the idea of treating most patients with MTC with selective RET inhibitors.

The approved standard treatment for advanced MTC is with multi-tyrosine kinase inhibitors cabozantinib and vandetanib irrespective of RET status. However, it is not known how well patients who are RET-positive respond to this kind of treatment.

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Clinical research has shown that selective RET inhibitors can be highly efficient for the treatment of MTC. 

Read more about MTC therapies

Here, a team of researchers from the German Study Group for Rare Malignant Tumors of the Thyroid and Parathyroid Glands led by Matthias Kroiss, MD, PhD, retrospectively analyzed 48 patients with advanced MTC who were treated with vandetanib and/or cabozantinib. The researchers looked at the patients’ RET oncogene variant status. They then estimated their rates of progression-free and overall survival.

The results showed that of the 48 patients, the majority (92%) had a germline or somatic RET variant. Of those who had a RET variant, more than half (66%) had the M918T variant. A total of 32 patients had a somatic variant, 2 of whom had more than 1 somatic variant. Additional variants were found in 1 patient who had a germline RET variant. Only 1 of the 48 patients had a pathogenic HRAS variant, and 3 patients had no variants at all.

For patients who were RET positive, the median overall survival was 53 months and the median progression-free survival was 21 months in first-line treatment while it was 18 months and 3.5 months respectively in second-line treatment.


Koehler VF, Adam P, Fuss CT, et al. Treatment of RET-positive advanced medullary thyroid cancer with multi-tyrosine kinase inhibitors—a retrospective multi-center registry analysis. Cancers 2022;14:3405. doi:10.3390/cancers14143405