RET Fusion: Joining the Ranks of Targetable Molecular Drivers in NSCLC

• Type of Material: Article
• Authors: Badi E Osta, Atlanta VA Medical Center; Suresh Ramalingam, Emory University
• Language: English
• Date: 2020-09-01
• Publisher: International Association for the Study of Lung Cancer.
• Publication Version: Final Published Version
• Copyright Statement: © 2020 by the International Association for the Study of Lung Cancer.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.jtocrr.2020.100050
• Title of Journal or Parent Work: JTO Clinical and Research Reports
• Volume: 1
• Issue: 3
• Start Page: 100050
• End Page: 100050
• Grant/Funding Information: This work was supported by National Cancer Institute P50 CA217691 and research grant provided by the Lee Foundation, Atlanta, Georgia. The views expressed in this article are those of the authors and do not necessarily reflect the position or policy of the Department of Veterans Affairs or the United States government.
• Keywords: Lung cancer; Selpercatinib; Pralsetinib; RET fusion; Targeted Therapy; Precision oncology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

The era of precision medicine has resulted in the identification of a number of genomic alterations that can be targeted with novel therapies. In lung adenocarcinomas, a histology structure that accounts for nearly 50% of all cases of lung cancer, and a number of genomic targets have been linked with effective targeted therapies. For patients with advanced-stage lung adenocarcinomas, molecular testing is now a standard part of diagnostic workup; for patients that have specific driver molecular events, targeted therapies have resulted in substantial improvement in efficacy without excessive toxicity. RET gene fusions are present in approximately 1% to 2% of NSCLC. It is emerging as a new targetable driver for this population. Despite sensitivity to platinum-based chemotherapy and conflicting small reports regarding the efficacy of immune checkpoint inhibitors, there have been limited treatment approaches for this subset of patients. Multiple nonselective RET tyrosine kinase inhibitors exhibited modest anti-RET activity with an increased off-target toxicity profile that often required dose interruption, reduction, or treatment cessation. Recently, novel selective RET inhibitors pralsetinib (BLU-667) and selpercatinib (LOXO-292) have exhibited promising clinical activity with low adverse effect profile in early clinical trials. These new agents are poised to represent a new hope for this special subgroup with unmet needs.