Treatment of Progressive Radioiodine-Refractory Papillary Thyroid Cancer Harbouring an Oncogenic RET Gene Fusion

This protocol defines the recommended first-line approach for a molecularly characterised subgroup: papillary thyroid carcinoma that has progressed despite radioiodine therapy and carries a confirmed oncogenic RET gene fusion.

Clinical scenario: Progressive radioiodine-refractory (RAIR) papillary thyroid carcinoma with a confirmed oncogenic RET gene fusion. In this setting, tumour genotyping identifies a targetable driver alteration that changes the treatment path from systemic chemotherapy or non-selective kinase blockade to dedicated RET-targeted therapy in the first line.

Treatment approach — partial overview

Management in this setting centres on oral, highly selective RET kinase inhibitor therapy. There is a preferred agent, and an alternative is available when the preferred option is not suitable. The full protocol specifies which agent is recommended, the clinical criteria guiding that choice, and what distinguishes the two options — accessible via the link below.

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References

DOI: 10.1177/10507256251363120

In patients with progressive RAIR DTC harboring an oncogenic RET fusion, RET-targeted therapy is recommended in the first line.

Selpercatinib is an oral highly specific and potent RET kinase inhibitor, with limited off-target activity against other kinases, especially VEGFR2.

Pralsetinib is another RET kinase-specific oral small molecule inhibitor, like selpercatinib, designed to have potent anti-RET activity with minimal off-RET kinase activity.

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