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J Clin Oncol. 2015 Mar 20;33(9):992-9. doi: 10.1200/JCO.2014.58.3302. Epub 2015 Feb 9.

Crizotinib therapy for advanced lung adenocarcinoma and a ROS1 rearrangement: results from the EUROS1 cohort.

Author information

1
Julien Mazières, Damien Rouvière, and Julie D. Milia, Hôpital Larrey, Centre Hospitalier Universitaire, Université Paul Sabatier; Thomas Filleron, Institut Universitaire du Cancer, Toulouse; Gérard Zalcman, Centre Hospitalier Universitaire, Université de Caen-Basse Normandie, Caen; Pamela Biondani and Benjamin Besse, Gustave Roussy, Villejuif; Fabrice Barlesi, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille; Hervé Léna, Centre Hospitalier Universitaire, Rennes; Isabelle Monnet, Centre Hospitalier Intercommunal de Créteil, Créteil; Luc Thiberville, Centre Hospitalier Universitaire, Rouen; Nicolas Pecuchet, Institut Curie, Paris, France; Lucio Crinò, Medica-Azienda Ospedaliera, Perugia; Federico Cappuzzo, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy; Anne-Marie C. Dingemans, Maastricht University Medical Center, Maastricht; Egbert F. Smit, VU University Medical Center, Amsterdam, the Netherlands; Sacha I. Rothschild, University Hospital Basel, Medical Oncology, Basel; Christian Spirig, Klinik St Anna; Joachim Diebold and Oliver Gautschi, Cantonal Hospital Luzern, Lucerne, Switzerland; Rafal Dziadziuszko, Gdansk Medical University, Gdansk, Poland; Jurgen Wolf and Roman K. Thomas, Center of Integrated Oncology Köln-Bonn, University Hospital Cologne, University of Cologne; Frauke Leenders and Roman K. Thomas, University of Cologne; Johannes M. Heuckmann, Blackfield AG, Cologne, Germany. mazieres.j@chu-toulouse.fr.
2
Julien Mazières, Damien Rouvière, and Julie D. Milia, Hôpital Larrey, Centre Hospitalier Universitaire, Université Paul Sabatier; Thomas Filleron, Institut Universitaire du Cancer, Toulouse; Gérard Zalcman, Centre Hospitalier Universitaire, Université de Caen-Basse Normandie, Caen; Pamela Biondani and Benjamin Besse, Gustave Roussy, Villejuif; Fabrice Barlesi, Aix-Marseille University, Assistance Publique Hôpitaux de Marseille, Marseille; Hervé Léna, Centre Hospitalier Universitaire, Rennes; Isabelle Monnet, Centre Hospitalier Intercommunal de Créteil, Créteil; Luc Thiberville, Centre Hospitalier Universitaire, Rouen; Nicolas Pecuchet, Institut Curie, Paris, France; Lucio Crinò, Medica-Azienda Ospedaliera, Perugia; Federico Cappuzzo, Istituto Toscano Tumori, Ospedale Civile, Livorno, Italy; Anne-Marie C. Dingemans, Maastricht University Medical Center, Maastricht; Egbert F. Smit, VU University Medical Center, Amsterdam, the Netherlands; Sacha I. Rothschild, University Hospital Basel, Medical Oncology, Basel; Christian Spirig, Klinik St Anna; Joachim Diebold and Oliver Gautschi, Cantonal Hospital Luzern, Lucerne, Switzerland; Rafal Dziadziuszko, Gdansk Medical University, Gdansk, Poland; Jurgen Wolf and Roman K. Thomas, Center of Integrated Oncology Köln-Bonn, University Hospital Cologne, University of Cologne; Frauke Leenders and Roman K. Thomas, University of Cologne; Johannes M. Heuckmann, Blackfield AG, Cologne, Germany.

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.

PMID:
25667280
DOI:
10.1200/JCO.2014.58.3302
[Indexed for MEDLINE]

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