Mazieres, Julien, Zalcman, Gerard, Crino, Lucio, Biondani, Pamela, Barlesi, Fabrice, Filleron, Thomas, Dingemans, Anne-Marie C., Lena, Herve, Monnet, Isabelle, Rothschild, Sacha I., Cappuzzo, Federico, Besse, Benjamin ORCID: 0000-0001-5090-8189, Thiberville, Luc, Rouviere, Damien, Dziadziuszko, Rafal ORCID: 0000-0001-8080-9843, Smit, Egbert F., Wolf, Jurgen, Spirig, Christian, Pecuchet, Nicolas ORCID: 0000-0002-3321-5791, Leenders, Frauke, Heuckmann, Johannes M., Diebold, Joachim, Milia, Julie D., Thomas, Roman K. and Gautschi, Oliver (2015). Crizotinib Therapy for Advanced Lung Adenocarcinoma and a ROS1 Rearrangement: Results From the EUROS1 Cohort. J. Clin. Oncol., 33 (9). S. 992 - 1002. ALEXANDRIA: AMER SOC CLINICAL ONCOLOGY. ISSN 1527-7755

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Abstract

Purpose Approximately 1% of lung adenocarcinomas are driven by oncogenic ROS1 rearrangement. Crizotinib is a potent inhibitor of both ROS1 and ALK kinase domains. Patients and Methods In the absence of a prospective clinical trial in Europe, we conducted a retrospective study in centers that tested for ROS1 rearrangement. Eligible patients had stage IV lung adenocarcinoma, had ROS1 rearrangement according to fluorescent in situ hybridization, and had received crizotinib therapy through an individual off-label use. Best response was assessed locally using RECIST (version 1.1). All other data were analyzed centrally. Results We identified 32 eligible patients. One patient was excluded because next-generation sequencing was negative for ROS1 fusion. Median age was 50.5 years, 64.5% of patients were women, and 67.7% were never-smokers. Thirty patients were evaluable for progression-free survival (PFS), and 29 patients were evaluable for best response. We observed four patients with disease progression, two patients with stable disease, and objective response in 24 patients, including five complete responses (overall response rate, 80%; disease control rate, 86.7%). Median PFS was 9.1 months, and the PFS rate at 12 months was 44%. No unexpected adverse effects were observed. Twenty-six patients received pemetrexed (either alone or in combination with platinum and either before or after crizotinib) and had a response rate of 57.7% and a median PFS of 7.2 months. Conclusion Crizotinib was highly active at treating lung cancer in patients with a ROS1 rearrangement, suggesting that patients with lung adenocarcinomas should be tested for ROS1. Prospective clinical trials with crizotinib and other ROS1 inhibitors are ongoing or planned. (C) 2015 by American Society of Clinical Oncology

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Mazieres, JulienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zalcman, GerardUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Crino, LucioUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Biondani, PamelaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Barlesi, FabriceUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Filleron, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dingemans, Anne-Marie C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lena, HerveUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Monnet, IsabelleUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rothschild, Sacha I.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cappuzzo, FedericoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Besse, BenjaminUNSPECIFIEDorcid.org/0000-0001-5090-8189UNSPECIFIED
Thiberville, LucUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rouviere, DamienUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dziadziuszko, RafalUNSPECIFIEDorcid.org/0000-0001-8080-9843UNSPECIFIED
Smit, Egbert F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolf, JurgenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Spirig, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pecuchet, NicolasUNSPECIFIEDorcid.org/0000-0002-3321-5791UNSPECIFIED
Leenders, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heuckmann, Johannes M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diebold, JoachimUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milia, Julie D.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Thomas, Roman K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Gautschi, OliverUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-404795
DOI: 10.1200/JCO.2014.58.3302
Journal or Publication Title: J. Clin. Oncol.
Volume: 33
Number: 9
Page Range: S. 992 - 1002
Date: 2015
Publisher: AMER SOC CLINICAL ONCOLOGY
Place of Publication: ALEXANDRIA
ISSN: 1527-7755
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
CLINICOPATHOLOGICAL ANALYSIS; ACQUIRED-RESISTANCE; NEVER-SMOKERS; HER2 MUTATION; CANCER; FUSION; PATIENT; RET; GLIOBLASTOMA; GENEMultiple languages
OncologyMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/40479

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