ESMO Updates the Guidelines for the Diagnosis of RET-Altered Cancer to Herald a New Era in Targeted Therapy

Abstract

The RET gene encodes a tyrosine kinase receptor that regulates cell survival and proliferation by triggering key downstream pathways.1 RET gene mutations and RET gene fusions are involved in the pathogenesis of lung, thyroid and other cancers. Recently, in 2021, the European Society for Medical Oncology (ESMO) has developed recommendations for the laboratory diagnosis of targetable RET rearrangements and mutations.2 Following the results from phase I/II clinical trials,3,4 selpercatinib, a RET tyrosine kinase inhibitor (TKI), received the FDA5 and Swissmedic6 authorization for the treatment of adult patients with RET fusion-positive non-small cell lung cancer (NSCLC) and advanced RET fusion-positive thyroid cancer who require systemic therapy and who have progressed after prior treatment. Selpercatinib is also indicated for the treatment of adults and adolescents ≥12 years old with advanced RET-mutated medullary thyroid carcinoma (MTC) who require systemic therapy and who have experienced progression after prior treatment with TKIs. In this clinical setting, the Food and Drug Administration (FDA) has recently approved another RET TKI, pralsetinib.7 In addition, the FDA also granted accelerated approval to pralsetinib for adult patients with metastatic RET fusion-positive NSCLC.8 This review aims to summarize the new ESMO recommendations for the laboratory diagnosis of RET-altered cancers and the clinical trial data that support the regulatory approvals of selpercatinib and pralsetinib for RET-altered NSCLC and thyroid cancer.

Keywords

• thyroid cancer
• nsclc
• pralsetinib
• selpercatinib
• ret inhibitors