ROS1 rearrangements in lung adenocarcinoma: prognostic impact, therapeutic options and genetic variability

While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. 1137 patients with adenocarcinoma of the lung wer...

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Bibliographic Details
Published in:	Oncotarget 2015-04, Vol.6 (12), p.10577-10585
Main Authors:	Scheffler, Matthias, Schultheis, Anne, Teixido, Cristina, Michels, Sebastian, Morales-Espinosa, Daniela, Viteri, Santiago, Hartmann, Wolfgang, Merkelbach-Bruse, Sabine, Fischer, Rieke, Schildhaus, Hans-Ulrich, Fassunke, Jana, Sebastian, Martin, Serke, Monika, Kaminsky, Britta, Randerath, Winfried, Gerigk, Ulrich, Ko, Yon-Dschun, Krüger, Stefan, Schnell, Roland, Rothe, Achim, Kropf-Sanchen, Cornelia, Heukamp, Lukas, Rosell, Rafael, Büttner, Reinhard, Wolf, Jürgen
Format:	Article
Language:	eng
Subjects:	Adenocarcinoma - drug therapy Adenocarcinoma - enzymology Adenocarcinoma - genetics Adenocarcinoma of Lung Adult Aged Clinical Research Paper Female Gene Rearrangement Genetic Variation Humans Lung Neoplasms - drug therapy Lung Neoplasms - enzymology Lung Neoplasms - genetics Male Middle Aged Prognosis Protein-Tyrosine Kinases - genetics Protein-Tyrosine Kinases - metabolism Proto-Oncogene Proteins - genetics Proto-Oncogene Proteins - metabolism Survival Analysis Treatment Outcome
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Summary:	While recent data show that crizotinib is highly effective in patients with ROS1 rearrangement, few data is available about the prognostic impact, the predictive value for different treatments, and the genetic heterogeneity of ROS1-positive patients. 1137 patients with adenocarcinoma of the lung were analyzed regarding their ROS1 status. In positive cases, next-generation sequencing (NGS) was performed. Clinical characteristics, treatments and outcome of these patients were assessed. Overall survival (OS) was compared with genetically defined subgroups of ROS1-negative patients. 19 patients of 1035 evaluable (1.8%) had ROS1-rearrangement. The median OS has not been reached. Stage IV patients with ROS1-rearrangement had the best OS of all subgroups (36.7 months, p < 0.001). 9 of 14 (64.2%) patients had at least one response to chemotherapy. Estimated mean OS for patients receiving chemotherapy and crizotinib was 5.3 years. Ten patients with ROS1-rearrangement (52.6%) harbored additional aberrations. ROS1-rearangement is not only a predictive marker for response to crizotinib, but also seems to be the one of the best prognostic molecular markers in NSCLC reported so far. In stage IV patients, response to chemotherapy was remarkable high and overall survival was significantly better compared to other subgroups including EGFR-mutated and ALK-fusion-positive NSCLC.
ISSN:	1949-2553 1949-2553