Partielles Ansprechen auf Crizotinib als Erstlinientherapie bei einem älteren männlichen Patienten mit ROS1-Translokations-positivem Bronchialkarzinom

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Abstract

Wir berichten hier über einen 90-jährigen männlichen Patienten mit ROS1-transloziertem Adenokarzinom der Lunge, der eine Erstlinientherapie mit Crizotinib erhielt. Nach 11-monatiger Behandlung waren ein vollständiges metabolisches Ansprechen laut <sup>18</sup>F-FDG-PET/CT-Scan sowie ein partielles Ansprechen nach RECIST-Kriterien zu verzeichnen. Dieser Fall deutet darauf hin, dass ROS1-Translokationen sich nicht auf junges Alter, weibliches Geschlecht und niedrige Tumorstadien beschränken. Außerdem zeigt der Fall exemplarisch, dass die Crizotinib-Therapie auch als Erstlinientherapie bei älteren, komorbiden Patienten wirksam und beherrschbar sein kann. Auf Grundlage unserer Ergebnisse empfehlen wir, ältere Patienten mit fortgeschrittenem Adenokarzinom der Lunge in molekulare Screenings für ROS1-Translokationen einzuschließen.

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Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.

Klarisa Rikova, Ailan Guo, Qingfu Zeng … (2008)

Despite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFRalpha and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers.

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ROS1 rearrangements define a unique molecular class of lung cancers.

Kristin Bergethon, Alice Shaw, Sai-Hong Ignatius Ou … (2012)

Chromosomal rearrangements involving the ROS1 receptor tyrosine kinase gene have recently been described in a subset of non-small-cell lung cancers (NSCLCs). Because little is known about these tumors, we examined the clinical characteristics and treatment outcomes of patients with NSCLC with ROS1 rearrangement. Using a ROS1 fluorescent in situ hybridization (FISH) assay, we screened 1,073 patients with NSCLC and correlated ROS1 rearrangement status with clinical characteristics, overall survival, and when available, ALK rearrangement status. In vitro studies assessed the responsiveness of cells with ROS1 rearrangement to the tyrosine kinase inhibitor crizotinib. The clinical response of one patient with ROS1-rearranged NSCLC to crizotinib was investigated as part of an expanded phase I cohort. Of 1,073 tumors screened, 18 (1.7%) were ROS1 rearranged by FISH, and 31 (2.9%) were ALK rearranged. Compared with the ROS1-negative group, patients with ROS1 rearrangements were significantly younger and more likely to be never-smokers (each P < .001). All of the ROS1-positive tumors were adenocarcinomas, with a tendency toward higher grade. ROS1-positive and -negative groups showed no difference in overall survival. The HCC78 ROS1-rearranged NSCLC cell line and 293 cells transfected with CD74-ROS1 showed evidence of sensitivity to crizotinib. The patient treated with crizotinib showed tumor shrinkage, with a near complete response. ROS1 rearrangement defines a molecular subset of NSCLC with distinct clinical characteristics that are similar to those observed in patients with ALK-rearranged NSCLC. Crizotinib shows in vitro activity and early evidence of clinical activity in ROS1-rearranged NSCLC.

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A genomics-based classification of human lung tumors.

(2013)

We characterized genome alterations in 1255 clinically annotated lung tumors of all histological subgroups to identify genetically defined and clinically relevant subtypes. More than 55% of all cases had at least one oncogenic genome alteration potentially amenable to specific therapeutic intervention, including several personalized treatment approaches that are already in clinical evaluation. Marked differences in the pattern of genomic alterations existed between and within histological subtypes, thus challenging the original histomorphological diagnosis. Immunohistochemical studies confirmed many of these reassigned subtypes. The reassignment eliminated almost all cases of large cell carcinomas, some of which had therapeutically relevant alterations. Prospective testing of our genomics-based diagnostic algorithm in 5145 lung cancer patients enabled a genome-based diagnosis in 3863 (75%) patients, confirmed the feasibility of rational reassignments of large cell lung cancer, and led to improvement in overall survival in patients with EGFR-mutant or ALK-rearranged cancers. Thus, our findings provide support for broad implementation of genome-based diagnosis of lung cancer.

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Journal

Journal ID (publisher-id): KKO

Journal ID (doi): 10.1159/issn.2296-5416

Title: Karger Kompass Onkologie

Publisher: S. Karger AG

ISSN (Print): 2296-5416

ISSN (Electronic): 2296-5386

Publication date Subscription-year: 2016

Publication date (Print): November 2016

Publication date (Electronic): 17 November 2016

Volume: 3

Issue: 2

Pages: 97-100

Affiliations

^aLungentumorzentrum Universität Göttingen and Göttingen Comprehensive Cancer Center (G-CCC), ^bDepartment of Hematology and Medical Oncology, ^cInstitute of Pathology, ^dDepartment of Radiology, and ^eDepartment of Nuclear Medicine, University Hospital Göttingen, Göttingen, Germany

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Publisher ID: 449192 Other ID: Karger Kompass Onkol 2016;3:97-100

DOI: 10.1159/000449192

SO-VID: cd298ddf-a33e-4301-bb56-ca9a10a9d063

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Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

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Partielles Ansprechen auf Crizotinib als Erstlinientherapie bei einem älteren männlichen Patienten mit ROS1-Translokations-positivem Bronchialkarzinom

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Abstract

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Karger: Oncology

Most cited references 7

Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer.

ROS1 rearrangements define a unique molecular class of lung cancers.

A genomics-based classification of human lung tumors.

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