RET Fusion-Positive Non-small Cell Lung Cancer: The Evolving Treatment Landscape

The objective of this narrative review is to summarize the efficacy and safety of available therapies for rearranged during transfection (RET) fusion-positive non-small cell lung cancer (NSCLC), including in patients with central nervous system (CNS) metastases. Background information is provided on RET rearrangements in NSCLC and the molecular testing options available as well as an overview of clinical guidelines for molecular testing, which recommend broad molecular testing, including for RET rearrangements. The efficacy and safety of potential treatments for RET fusion-positive NSCLC, including multikinase inhibitors, RET-selective inhibitors, pemetrexed-based therapy, and immunotherapies are reviewed from Phase I/II and `real-world' studies, alongside an overview of primary and secondary resistance mechanisms. The RET-selective inhibitors, selpercatinib and pralsetinib, are preferred first-line therapy options for patients with RET fusion-positive metastatic NSCLC and are recommended as subsequent therapy if RET inhibitors have not been used in the first-line setting. This review summarizes the efficacy and safety of available therapies for RET fusion-positive non-small cell lung cancer, including in patients with central nervous system metastases.

Automated summary

This narrative review aims to summarize the efficacy and safety of available therapies for RET fusion-positive non-small cell lung cancer (NSCLC) and central nervous system (CNS) metastases. It provides background information on RET rearrangements in NSCLC and molecular testing options, along with an overview of clinical guidelines for broad molecular testing. The review discusses the efficacy and safety of potential treatments, including multikinase inhibitors, RET-selective inhibitors, pemetrexed-based therapy, and immunotherapies, and highlights RET-selective inhibitors as preferred first-line therapy options for RET fusion-positive metastatic NSCLC.