Selpercatinib in the treatment of thyroid cancer

Area of Science:

• Oncology
• Molecular Biology
• Pharmacology

Background:

• Thyroid cancer encompasses various subtypes, with RET alterations driving specific aggressive forms like medullary thyroid cancer (MTC) and differentiated thyroid cancer (DTC).
• Traditional treatments often involve less specific multikinase inhibitors, posing challenges in efficacy and tolerability for patients with RET-driven thyroid cancers.
• The development of targeted therapies is crucial for improving outcomes in these challenging malignancies.

Purpose of the Study:

• To review the molecular basis of RET-driven thyroid cancers.
• To evaluate the clinical efficacy, safety, and tolerability of selpercatinib, a selective RET inhibitor.
• To discuss the therapeutic landscape and the role of selpercatinib in current treatment guidelines.

Main Methods:

• Systematic review of clinical trial data (LIBRETTO-001, LIBRETTO-531) and real-world evidence.
• Analysis of molecular underpinnings of RET alterations in thyroid cancer.
• Comparison of selpercatinib with existing multikinase inhibitors.

Main Results:

• Selpercatinib demonstrated high overall response rates: >84% in treatment-naïve RET-mutant MTC and 95% in RET fusion-positive DTC.
• Superior efficacy, safety, and tolerability compared to less specific multikinase inhibitors.
• Real-world studies confirm sustained long-term benefits across diverse patient populations.

Conclusions:

• Selpercatinib is a highly effective and well-tolerated targeted therapy for RET-driven thyroid cancers.
• It is recommended as a first-line treatment for advanced RET-mutant MTC and a second-line option for radioiodine-refractory DTC (RAIR DTC).
• Selpercatinib represents a paradigm shift in managing these specific thyroid cancer subtypes.