Gautschi, Oliver, Milia, Julie, Filleron, Thomas, Wolf, Juergen, Carbone, David P., Owen, Dwight ORCID: 0000-0002-6598-4886, Camidge, Ross, Narayanan, Vignhesh, Doebele, Robert C. ORCID: 0000-0001-6728-6857, Besse, Benjamin ORCID: 0000-0001-5090-8189, Remon-Masip, Jordi, Janne, Pasi A., Awad, Mark M., Peled, Nir, Byoung, Chul-Cho, Karp, Daniel D., Van Den Heuvel, Michael, Wakelee, Heather A., Neal, Joel W., Mok, Tony S. K., Yang, James C. H., Ou, Sai-Hong Ignatius, Pall, Georg, Froesch, Patrizia, Zalcman, Gerard, Gandara, David R., Riess, JonathanW., Velcheti, Vamsidhar, Zeidler, Kristin, Diebold, Joachim, Frueh, Martin, Michels, Sebastian, Monnet, Isabelle, Popat, Sanjay ORCID: 0000-0003-2087-4963, Rosell, Rafael, Karachaliou, Niki, Rothschild, Sacha I., Shih, Jin-Yuan, Warth, Arne, Muley, Thomas, Cabillic, Florian ORCID: 0000-0001-7204-5652, Mazieres, Julien and Drilon, Alexander (2017). Targeting RET in Patients With RET-Rearranged Lung Cancers: Results From the Global, Multicenter RET Registry. J. Clin. Oncol., 35 (13). S. 1403 - 1414. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

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. (C) 2017 by American Society of Clinical Oncology

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Gautschi, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milia, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Filleron, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JuergenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carbone, David P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, DwightUNSPECIFIEDorcid.org/0000-0002-6598-4886UNSPECIFIED
Camidge, RossUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Narayanan, VignheshUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doebele, Robert C.UNSPECIFIEDorcid.org/0000-0001-6728-6857UNSPECIFIED
Besse, BenjaminUNSPECIFIEDorcid.org/0000-0001-5090-8189UNSPECIFIED
Remon-Masip, JordiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Janne, Pasi A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Awad, Mark M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peled, NirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Byoung, Chul-ChoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karp, Daniel D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Van Den Heuvel, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wakelee, Heather A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Neal, Joel W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mok, Tony S. K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Yang, James C. H.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ou, Sai-Hong IgnatiusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pall, GeorgUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Froesch, PatriziaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zalcman, GerardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gandara, David R.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riess, JonathanW.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velcheti, VamsidharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zeidler, KristinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diebold, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Frueh, MartinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michels, SebastianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monnet, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Popat, SanjayUNSPECIFIEDorcid.org/0000-0003-2087-4963UNSPECIFIED
Rosell, RafaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Karachaliou, NikiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rothschild, Sacha I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shih, Jin-YuanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Warth, ArneUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Muley, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cabillic, FlorianUNSPECIFIEDorcid.org/0000-0001-7204-5652UNSPECIFIED
Mazieres, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Drilon, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-233338
DOI: 10.1200/JCO.2016.70.9352
Journal or Publication Title: J. Clin. Oncol.
Volume: 35
Number: 13
Page Range: S. 1403 - 1414
Date: 2017
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
KIF5B-RET FUSIONS; OPEN-LABEL; ADENOCARCINOMA; CABOZANTINIB; IDENTIFICATION; THERAPY; COHORT; GENE; PROTOONCOGENE; VANDETANIBMultiple languages
OncologyMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23333

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