Universität zu Köln

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

Full text not available from this repository.

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:	Creators Email ORCID ORCID Put Code Drilon, Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED Lin, Jessica J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Filleron, Thomas UNSPECIFIED UNSPECIFIED UNSPECIFIED Ni, Ai UNSPECIFIED orcid.org/0000-0003-3002-3556 UNSPECIFIED Milia, Julie UNSPECIFIED UNSPECIFIED UNSPECIFIED Bergagnini, Isabella UNSPECIFIED UNSPECIFIED UNSPECIFIED Hatzoglou, Vaios UNSPECIFIED UNSPECIFIED UNSPECIFIED Velcheti, Vamsidhar UNSPECIFIED UNSPECIFIED UNSPECIFIED Offin, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Bob UNSPECIFIED UNSPECIFIED UNSPECIFIED Carbone, David P. UNSPECIFIED UNSPECIFIED UNSPECIFIED Besse, Benjamin UNSPECIFIED orcid.org/0000-0001-5090-8189 UNSPECIFIED Mok, Tony UNSPECIFIED UNSPECIFIED UNSPECIFIED Awad, Mark M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Wolf, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Owen, Dwight UNSPECIFIED orcid.org/0000-0002-6598-4886 UNSPECIFIED Camidge, D. Ross UNSPECIFIED UNSPECIFIED UNSPECIFIED Riely, Gregory J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Peled, Nir UNSPECIFIED UNSPECIFIED UNSPECIFIED Kris, Mark G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mazieres, Julien UNSPECIFIED UNSPECIFIED UNSPECIFIED Gainor, Justin F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Gautschi, Oliver UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language TARGETING RET; OPEN-LABEL; PHASE-2; VANDETANIB Multiple languages Oncology; Respiratory System Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/17162