Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry
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Open Access
- 1 May 2017
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 35 (13), 1403-1410
- https://doi.org/10.1200/jco.2016.70.9352
Abstract
In addition to prospective trials for non–small-cell lung cancers (NSCLCs) that are driven by less common genomic alterations, registries provide complementary information on patient response to targeted therapies. Here, we present the results of an international registry of patients with RET-rearranged NSCLCs, providing the largest data set, to our knowledge, on outcomes of RET-directed therapy thus far. A global, multicenter network of thoracic oncologists identified patients with pathologically confirmed NSCLC that harbored a RET rearrangement. Molecular profiling was performed locally by reverse transcriptase polymerase chain reaction, fluorescence in situ hybridization, or next-generation sequencing. Anonymized data—clinical, pathologic, and molecular features—were collected centrally and analyzed by an independent statistician. Best response to RET tyrosine kinase inhibition administered outside of a clinical trial was determined by RECIST v1.1. By April 2016, 165 patients with RET-rearranged NSCLC from 29 centers across Europe, Asia, and the United States were accrued. Median age was 61 years (range, 29 to 89 years). The majority of patients were never smokers (63%) with lung adenocarcinomas (98%) and advanced disease (91%). The most frequent rearrangement was KIF5B-RET (72%). Of those patients, 53 received one or more RET tyrosine kinase inhibitors in sequence: cabozantinib (21 patients), vandetanib (11 patients), sunitinib (10 patients), sorafenib (two patients), alectinib (two patients), lenvatinib (two patients), nintedanib (two patients), ponatinib (two patients), and regorafenib (one patient). The rate of any complete or partial response to cabozantinib, vandetanib, and sunitinib was 37%, 18%, and 22%, respectively. Further responses were observed with lenvantinib and nintedanib. Median progression-free survival was 2.3 months (95% CI, 1.6 to 5.0 months), and median overall survival was 6.8 months (95% CI, 3.9 to 14.3 months). Available multikinase inhibitors had limited activity in patients with RET-rearranged NSCLC in this retrospective study. Further investigation of the biology of RET-rearranged lung cancers and identification of new targeted therapeutics will be required to improve outcomes for these patients.Keywords
This publication has 44 references indexed in Scilit:
- Lung Cancer That Harbors an HER2 Mutation: Epidemiologic Characteristics and Therapeutic PerspectivesJournal of Clinical Oncology, 2013
- Identification of RET gene fusion by exon array analyses in “pan-negative” lung cancer from never smokersCell Research, 2012
- Cabozantinib (XL184), a Novel MET and VEGFR2 Inhibitor, Simultaneously Suppresses Metastasis, Angiogenesis, and Tumor GrowthMolecular Cancer Therapeutics, 2011
- Regorafenib (BAY 73‐4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activityInternational Journal of Cancer, 2010
- Transcript Level Modulates the Inherent Oncogenicity of RET/PTC OncoproteinsCancer Research, 2009
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- RET tyrosine kinase signaling in development and cancerCytokine & Growth Factor Reviews, 2005
- Proximity of Chromosomal Loci That Participate in Radiation-Induced Rearrangements in Human CellsScience, 2000
- Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor RetNature, 1994
- Activation of a novel human transforming gene, ret, by DNA rearrangementCell, 1985