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Ref Type Journal Article
PMID (28447912)
Authors Gautschi O, Milia J, Filleron T, Wolf J, Carbone DP, Owen D, Camidge R, Narayanan V, Doebele RC, Besse B, Remon-Masip J, Janne PA, Awad MM, Peled N, Byoung CC, Karp DD, Van Den Heuvel M, Wakelee HA, Neal JW, Mok TSK, Yang JCH, Ou SI, Pall G, Froesch P, Zalcman G, Gandara DR, Riess JW, Velcheti V, Zeidler K, Diebold J, Früh M, Michels S, Monnet I, Popat S, Rosell R, Karachaliou N, Rothschild SI, Shih JY, Warth A, Muley T, Cabillic F, Mazières J, Drilon A
Title Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry.
Journal Vol Issue Date Pages Journal Short Title
Journal of clinical oncology : official journal of the American Society of Clinical Oncology 35 13 2017 May 01 1403-1410 J Clin Oncol
URL
Abstract Text Purpose 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. Methods 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. Results 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). Conclusion 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
RET rearrange lung non-small cell carcinoma predicted - sensitive Sunitinib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/9, all partial responses), and stable disease in 33% (3/9) of patients following Sutent (sunitinib) treatment (PMID: 28447912). 28447912
RET rearrange lung non-small cell carcinoma sensitive Cabozantinib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 37% (7/19), with complete response in 5% (1/19) and partial response in 32% (6/19) of patients, and stable disease in 26% (5/19) of patients following Cometriq (cabozantinib) treatment (PMID: 28447912). 28447912
RET rearrange lung non-small cell carcinoma sensitive Vandetanib Clinical Study Actionable In a clinical study, analysis of patients with RET-rearranged non-small cell lung cancer treated with RET inhibitors demonstrated a response rate of 18% (2/11, all partial responses) and stable disease in 27% (3/11) of patients following Caprelsa (vandetanib) treatment (PMID: 28447912). 28447912