Drilon, Alexander, Lin, Jessica J., Filleron, Thomas, Ni, Ai ORCID: 0000-0003-3002-3556, Milia, Julie, Bergagnini, Isabella, Hatzoglou, Vaios, Velcheti, Vamsidhar, Offin, Michael, Li, Bob, Carbone, David P., Besse, Benjamin ORCID: 0000-0001-5090-8189, Mok, Tony, Awad, Mark M., Wolf, Jurgen, Owen, Dwight ORCID: 0000-0002-6598-4886, Camidge, D. Ross, Riely, Gregory J., Peled, Nir, Kris, Mark G., Mazieres, Julien, Gainor, Justin F. and Gautschi, Oliver (2018). Frequency of Brain Metastases and Multikinase Inhibitor Outcomes in Patients With RET-Rearranged Lung Cancers. J. Thorac. Oncol., 13 (10). S. 1595 - 1602. NEW YORK: ELSEVIER SCIENCE INC. ISSN 1556-1380

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Abstract

Introduction: In ret proto-oncogene (RET)-rearranged lung cancers, data on the frequency of brain metastases and, in particular, the outcomes of multikinase inhibitor therapy in patients with intracranial disease are not well characterized. Methods: A global, multi-institutional registry (cohort A, n = 114) and a bi-institutional data set (cohort B, n = 71) of RET-rearranged lung cancer patients were analyzed. Patients were eligible if they had stage IV lung cancers harboring a RET rearrangement by local testing. The incidence of brain metastases and outcomes with multikinase inhibitor therapy were determined. Results: The frequency of brain metastases at the time of diagnosis of stage IV disease was 25% (95% confidence interval [CI]: 18%-32%) in all patients from both cohorts. The lifetime prevalence of brain metastasis in stage IV disease was 46% (95% CI: 34%-58%) in patients for whom longitudinal data was available. The cumulative incidence of brain metastases was significantly different (p = 0.0039) between RET-, ROS1-, and ALK receptor tyrosine kinase (ALK)-rearranged lung cancers, with RET intermediate between the other two groups. Although intracranial response data was not available in cohort A, the median progression-free survival of multikinase inhibitor therapy (cabozantinib, vandetanib, or sunitinib) in patients with brain metastases was 2.1 months (95% CI: 1.3-2.9 months, n = 10). In cohort B, an intracranial response was observed in 2 of 11 patients (18%) treated with cabozantinib, vandetanib (+/- everolimus), ponatinib, or alectinib; the median overall progression-free survival (intracranial and extracranial) was 3.9 months (95% CI: 2.0-4.9 months). Conclusions: Brain metastases occur frequently in RET-rearranged lung cancers, and outcomes with multikinase inhibitor therapy in general are suboptimal. Novel RET-directed targeted therapy strategies are needed. (C) 2018 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Drilon, AlexanderUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lin, Jessica J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Filleron, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ni, AiUNSPECIFIEDorcid.org/0000-0003-3002-3556UNSPECIFIED
Milia, JulieUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bergagnini, IsabellaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hatzoglou, VaiosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Velcheti, VamsidharUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Offin, MichaelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, BobUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Carbone, David P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Besse, BenjaminUNSPECIFIEDorcid.org/0000-0001-5090-8189UNSPECIFIED
Mok, TonyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Awad, Mark M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Owen, DwightUNSPECIFIEDorcid.org/0000-0002-6598-4886UNSPECIFIED
Camidge, D. RossUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riely, Gregory J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peled, NirUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kris, Mark G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Mazieres, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gainor, Justin F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gautschi, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-171624
DOI: 10.1016/j.jtho.2018.07.004
Journal or Publication Title: J. Thorac. Oncol.
Volume: 13
Number: 10
Page Range: S. 1595 - 1602
Date: 2018
Publisher: ELSEVIER SCIENCE INC
Place of Publication: NEW YORK
ISSN: 1556-1380
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
TARGETING RET; OPEN-LABEL; PHASE-2; VANDETANIBMultiple languages
Oncology; Respiratory SystemMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/17162

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