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J Thorac Oncol. 2019 Apr 9. pii: S1556-0864(19)30276-X. doi: 10.1016/j.jtho.2019.03.020. [Epub ahead of print]

Safety and efficacy of crizotinib in patients with advanced or metastatic ROS1-rearranged lung cancer (EUCROSS): A European phase 2 clinical trial.

Author information

1
Lung Cancer Group Cologne, Department I for Internal Medicine and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
2
Department for Oncology, Alicante University Hospital-ISABIAL, Pintor Baeza, 11, 03010 Alicante, Spain.
3
Institute of Pathology, University Hospital Goettingen, Robert-Koch-Strasse 40, 37075 Göttingen, Germany and Targos Molecular Pathology, Germaniastrasse 7, 34119 Kassel, Germany.
4
Institute of Medical Statistics and Computational Biology, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
5
Department of Hematology and Oncology, University Hospital of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany.
6
Vall d'Hebron University Hospital, Vall d'Hebron Institute of Oncology, Passeig de la Vall d'Hebron, 119-129, 08035 Barcelona, Spain.
7
Department of Pneumology, Protestant Lung Hospital Berlin, Lindenberger Weg 27, 13125 Berlin, Germany.
8
Complejo Hospitalario Universitario Insular Materno-Infantil de Gran Canaria, Universidad de Las Palmas de Gran Canaria, Avenida Marítima del Sur, s/n, 35016 Las Palmas de Gran Canaria, Spain.
9
Thoraxonkologie, Thoraxklinik, Röntgenstr. 1, 69126 Heidelberg, Germany.
10
Servei d'Oncologia Mèdica, Institut Català d'Oncologia Badalona-Hospital Germans Trias i Pujol, Carretera de Canyet, s/n, 08916 Badalona, Spain.
11
Department for Medical Oncology, Clínica Universidad de Navarra, Calle Marquesado de Sta. Marta, 1, 28027 Madrid, Spain; prior affiliation during the trial: Hospital Universitario Virgen del Rocío, Avda. Manuel Siurot, S/n, 41013 Sevilla, Spain.
12
Department for Oncology, Maastricht University Medical Center, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands.
13
Spanish Lung Cancer Group, Av. Meridiana, 358 6a planta, 08027 Barcelona, Spain.
14
Lung Cancer Group Cologne, Institute of Pathology and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
15
Institue of Hematopatholgy Hamburg,Fangdieckstr. 75 A, 22547 Hamburg, Germany and Lung Cancer Network NOWEL, Georgstraße 12, 26121 Oldenburg, Germany.
16
Hospital Clínico Universitario de Valencia, Av. de Blasco Ibáñez, 17, 46010 València.
17
NEO New Oncology GmbH, Gottfried-Hagen-Straße 20, 51105 Cologne, Germany.
18
Department of Radiology, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany.
19
Department for Thoracic Oncology, Airway Research Center North (ARCN), German Center for Lung Research, LungenClinic Grosshansdorf, Wöhrendamm 80, 22927 Großhansdorf, Germany.
20
University Hospital Basel, Department Internal Medicine, Medical Oncology, Petersgraben 4, 4031 Basel, Switzerland.
21
Clinical Trials Centre Cologne (CTCC) Medical Faculty, University of Cologne, Gleueler Str. 269, 50935 Cologne, Germany.
22
Department of Thoracic Oncology, Netherlands Cancer Institute, Plesmanlaan 121 1066CX, Amsterdam, The Netherlands.
23
Department of Medical Oncology, Hospital Universitario Puerta de Hierro de Majadahonda, Calle Manuel de Falla, 1, 28222 Majadahonda, Spain.
24
Germans Trias i Pujol Research Institute (IGTP), Camí de les Escoles, s/n, 08916 Badalona, Spain and Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, C/ Sabino Arana 5-19, 08028 Barcelona, Spain.
25
Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Badalona, Spain and Germans Trias i Pujol Research Institute (IGTP), Carretera de Canyet s/n. 08916 Badalona, Spain and and Institute of Oncology Rosell (IOR), University Hospital Sagrat Cor, C/ Sabino Arana 5-19, 08028 Barcelona, Spain.
26
Lung Cancer Group Cologne, Department I for Internal Medicine and Center for Integrated Oncology Cologne/Bonn, University Hospital Cologne, Kerpener Str. 62, 50937 Cologne, Germany. Electronic address: juergen.wolf@uk-koeln.de.

Abstract

INTRODUCTION:

ROS1 rearrangements are found in 1% of lung cancer patients. Therapeutic efficacy of crizotinib in this subset has been demonstrated in early phase trials in the US and East Asia. Here we present data on efficacy and safety of a prospective phase 2 trial evaluating crizotinib in European ROS1-positive patients (EUCROSS).

PATIENTS AND METHODS:

Trial design: multi-centre, single arm phase 2 trial (Clinicaltrial.gov identifier: NCT02183870). Key eligibility criteria: ≥18 years of age, advanced/metastatic lung cancer, centrally confirmed ROS1-rearranged (fluorescence-in situ hybridisation).

TREATMENT:

250 mg crizotinib twice daily. Primary endpoint: investigator-assessed objective response rate (ORR, Response Evaluation Criteria in Solid Tumors, version 1.1). Key secondary endpoints: progression-free survival (PFS), overall survival, efficacy by independent radiologic review (IRR), safety, health-related quality of life, molecular characterization of tumour tissue.

RESULTS:

Thirty-four patients received treatment. Four patients were excluded from efficacy analysis. Investigator ORR was 70% (95% CI, 51-85; 21 of 30 patients) and median PFS was 20.0 months (95% CI, 10.1-not reached). Two patients with ROS1 wild-type sequences assessed by DNA sequencing had progression as best response. CD74-ROS1-positive patients had a trend towards a higher ORR and longer median PFS. TP53-co-mutant patients had a significantly shorter median PFS than wild-type patients (7.0 months, 95% CI, 1.7-20.0 vs 24.1 months, 95% CI, 10.1-not reached; P=0.022). Treatment-related adverse events were documented in 33 of 34 patients (97%).

CONCLUSION:

Crizotinib is highly effective and safe in ROS1-rearranged lung cancer patients. ROS1-/TP53-co-aberrant patients had a significantly worse outcome compared to TP53 wild-type patients.

PMID:
30978502
DOI:
10.1016/j.jtho.2019.03.020

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