Targeting RET in patients with RET-rearranged lung cancers: Results from the global, multicenter RET registry

Oliver Gautschi, Julie Milia, Thomas Filleron, Juergen Wolf, David P. Carbone, Dwight Owen, Ross Camidge, Vignhesh Narayanan, Robert C. Doebele, Benjamin Besse, Jordi Remon-Masip, Pasi A. Janne, Mark M. Awad, Nir Peled, Chul Cho Byoung, Daniel D. Karp, Michael Van Den Heuvel, Heather A. Wakelee, Joel W. Neal, Tony S.K. MokJames C.H. Yang, Sai Hong Ignatius Ou, Georg Pall, Patrizia Froesch, Gérard Zalcman, David R. Gandara, Jonathan W. Riess, Vamsidhar Velcheti, Kristin Zeidler, Joachim Diebold, Martin Früh, Sebastian Michels, Isabelle Monnet, Sanjay Popat, Rafael Rosell, Niki Karachaliou, Sacha I. Rothschild, Jin Yuan Shih, Arne Warth, Thomas Muley, Florian Cabillic, Julien Mazières, Alexander Drilon

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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 nextgeneration 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.

Original languageEnglish
Pages (from-to)1403-1410
Number of pages8
JournalJournal of Clinical Oncology
Volume35
Issue number13
DOIs
Publication statusPublished - 2017 May 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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    Gautschi, O., Milia, J., Filleron, T., Wolf, J., Carbone, D. P., Owen, D., Camidge, R., Narayanan, V., Doebele, R. C., Besse, B., Remon-Masip, J., Janne, P. A., Awad, M. M., Peled, N., Byoung, C. C., Karp, D. D., Van Den Heuvel, M., Wakelee, H. A., Neal, J. W., ... Drilon, A. (2017). Targeting RET in patients with RET-rearranged lung cancers: Results from the global, multicenter RET registry. Journal of Clinical Oncology, 35(13), 1403-1410. https://doi.org/10.1200/JCO.2016.70.9352